Therapeutic Potential of 5-HT2C Receptor Agonists for Addictive Disorders

ACS Chemical Neuroscience

Volumn 6, Issue 7, 2015, Pages 1071-1088

  Higgins, Guy A ^a,b   Fletcher, Paul J ^b,c  

^a InterVivo Solutions Inc   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

Author keywords

5 HT2C receptor; addiction; impulsivity; lorcaserin; nicotine dependence; obesity; Serotonin

Indexed keywords

DEXFENFLURAMINE; DRUGS USED IN THE TREATMENT OF ADDICTION; LORCASERIN; SEROTONIN; SEROTONIN 2C AGONIST; SEROTONIN 2C RECEPTOR; SEROTONIN UPTAKE INHIBITOR; ANTIOBESITY AGENT; SEROTONIN 2 AGONIST;

ADDICTION; ALCOHOLISM; ARTICLE; BEHAVIOR CONTROL; COMPARATIVE EFFECTIVENESS; DRUG DEPENDENCE; DRUG DEPENDENCE TREATMENT; DRUG EFFICACY; DRUG MECHANISM; DRUG SELECTIVITY; EVIDENCE BASED PRACTICE; FEEDING; FOOD ADDICTION; HUMAN; IMPULSIVENESS; INTRINSIC ACTIVITY; MEDICAL SOCIETY; META ANALYSIS (TOPIC); MOTIVATION; NONHUMAN; OBESITY; OBSESSIVE COMPULSIVE DISORDER; PATHOLOGICAL GAMBLING; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PSYCHOPHARMACOLOGY; PSYCHOPHARMACOTHERAPY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REINFORCEMENT; REWARD; SEROTONIN RELEASE; SEROTONINERGIC TRANSMISSION; SMOKING CESSATION; SUBSTANCE ABUSE; TOBACCO DEPENDENCE; WEIGHT GAIN; ANIMAL; BEHAVIOR, ADDICTIVE; METABOLISM; SUBSTANCE-RELATED DISORDERS;

ANIMALIA;

ANIMALS; ANTI-OBESITY AGENTS; BEHAVIOR, ADDICTIVE; HUMANS; OBESITY; SEROTONIN; SEROTONIN 5-HT2 RECEPTOR AGONISTS; SEROTONIN UPTAKE INHIBITORS; SUBSTANCE-RELATED DISORDERS;

EID: 84937044120     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.5b00025     Document Type: Article

References (248)

1. Holden, C. (2001) "Behavioral" addictions: do they exist? Science 294, 980-982
2. Blundell, J. E. (1986) Serotonin manipulations and the structure of feeding behavior Appetite 7, 39-56
3. Garattini, S., Mennini, T., and Samanin, R. (1989) Reduction of food intake by manipulation of central serotonin. Current experimental results Br. J. Psychiatry 8, 41-51
4. Leibowitz, S. F. (1990) The role of serotonin in eating disorders Drugs 39, 33-48
5. Yu, D. S., Smith, F. L., Smith, D. G., and Lyness, W. H. (1986) Fluoxetine-induced attenuation of amphetamine self-administration in rats Life Sci. 39, 1383-1388
6. Smith, F. L., Yu, D. S., Smith, D. G., Leccese, A. P., and Lyness, W. H. (1986) Dietary tryptophan supplements attenuate amphetamine self-administration in the rat Pharmacol., Biochem. Behav. 25, 849-855
7. Gill, K. and Amit, Z. (1989) Serotonin uptake blockers and voluntary alcohol consumption. A review of recent studies Recent Dev Alcohol. 7, 225-248
8. Carroll, M. E., Lac, S. T., Asencio, M., and Kragh, R. (1990) Fluoxetine reduces intravenous cocaine self-administration in rats Pharmacol., Biochem. Behav. 35, 237-244
9. Higgins, G. A., Tomkins, D. M., Fletcher, P. J., and Sellers, E. M. (1992) Effect of drugs influencing 5-HT function on ethanol drinking and feeding behaviour in rats: studies using a drinkometer system Neurosci. Biobehav. Rev. 16, 535-552
10. Sellers, E. M., Higgins, G. A., and Sobell, M. B. (1992) 5-HT and alcohol abuse Trends Pharmacol. Sci. 13, 69-75
11. Peltier, R. and Schenk, S. (1993) Effects of serotonergic manipulations on cocaine self-administration in rats Psychopharmacology 110, 390-394
12. 3 receptor antagonists and the indirect 5-HT agonist, dexfenfluramine, on heroin self-administration in rats Psychopharmacology 114, 611-619
13. Müller, C. P. and Homberg, J. R. (2015) The role of serotonin in drug use and addiction Behav. Brain Res. 277C, 146-192
14. LeMarquand, D., Pihl, R. O., and Benkelfat, C. (1994) Serotonin and alcohol intake, abuse, and dependence: clinical evidence Biol. Psychiatry 36, 326-337
15. Kranzler, H. R., Burleson, J. A., Korner, P., Del Boca, F. K., Bohn, M. J., and Brown, J. (1995) Placebo-controlled trial of fluoxetine as an adjunct to relapse prevention in alcoholics Am. J. Psychiatry 152, 391-397
16. Pettinati, H. M., Volpicelli, J. R., Luck, G., Kranzler, H. R., Rukstalis, M. R., and Cnaan, A. (2001) Double-blind clinical trial of sertraline treatment for alcohol dependence J. Clin. Psychopharmacol. 21, 143-153
17. Johnson, B. A. (2008) Update on neuropharmacological treatments for alcoholism: scientific basis and clinical findings Biochem. Pharmacol. 75, 34-56
18. Fletcher, P. J., Lê, A. D., and Higgins, G. A. (2008) Serotonin receptors as potential targets for modulation of nicotine use and dependence Prog. Brain Res. 172, 361-383
19. Moeller, F. G., Schmitz, J. M., Steinberg, J. L., Green, C. M., Reist, C., Lai, L. Y., Swann, A. C., and Grabowski, J. (2007) Citalopram combined with behavioral therapy reduces cocaine use: a double-blind, placebo-controlled trial Am. J. Drug Alcohol Abuse 33, 367-378
20. Grabowski, J., Rhoades, H., Elk, R., Schmitz, J., Davis, C., Creson, D., and Kirby, K. (1995) Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: two placebo-controlled double-blind trials J. Clin. Psychopharmacol. 15, 163-174
21. Batki, S. L., Washburn, A. M., Delucchi, K., and Jones, R. T. (1996) A controlled trial of fluoxetine in crack cocaine dependence Drug Alcohol Depend. 41, 137-142
22. Ciraulo, D. A., Sarid-Segal, O., Knapp, C. M., Ciraulo, A. M., LoCastro, J., Bloch, D. A., Montgomery, M. A., Leiderman, D. B., and Elkashef, A. (2005) Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence Addiction 100, 12-22
23. Weintraub, M., Hasday, J. D., Mushlin, A. I., and Lockwood, D. H. (1984) A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination Arch. Int. Med. 144, 1143-1148
24. Guy-Grand, B., Apfelbaum, M., Crepaldi, G., Gries, A., Lefebvre, P., and Turner, P. (1989) International trial of long-term dexfenfluramine in obesity Lancet 2, 1142-1145
25. Turner, P. (1990) Dexfenfluramine. Its place in weight control Drugs 39, 53-62
26. Guy-Grand, B. (1992) Clinical studies with d -fenfluramine Am. J. Clin. Nutr. 55, 173S-176S
27. Carvajal, A., García del Pozo, J., Martín de Diego, I., Rueda de Castro, A. M., and Velasco, A. (2000) Efficacy of fenfluramine and dexfenfluramine in the treatment of obesity: a meta-analysis Methods Find. Exp. Clin. Pharmacol. 22, 285-290
28. Haddock, C. K., Poston, W. S., Dill, P. L., Foreyt, J. P., and Ericsson, M. (2002) Pharmacotherapy for obesity: a quantitative analysis of four decades of published randomized clinical trials Int. J. Obes. Relat. Metab. Disord. 26, 262-273
29. Krasner, N., Moore, M. R., Goldberg, A., Booth, J. C., Frame, A. H., and McLaren, A. D. (1976) A trial of fenfluramine in the treatment of the chronic alcoholic patient Br. J. Psychiatry 128, 346-353
30. Buydens-Branchey, L., Branchey, M., Hudson, J., Rothman, M., Fergeson, P., and McKernin, C. (1998) Effect of fenfluramine challenge on cocaine craving in addicted male users Am. J. Addict. 7, 142-155
31. Romach, M. K., Sellers, E. M., Kaplan, H. L., Somer, G. R., and Gomez-Mancilla, B. (2000) Efficacy of dexfenfluramine in the treatment of alcohol dependence Alcohol.: Clin. Exp. Res. 24, 1534-1541
32. Li, Z., Maglione, M., Tu, W., Mojica, W., Arterburn, D., Shugarman, L. R., Hilton, L., Suttorp, M., Solomon, V., Shekelle, P. G., and Morton, S. C. (2005) Meta-analysis: pharmacologic treatment of obesity Ann. Int. Med. 142, 532-46
33. Halford, J. C., Harrold, J. A., Boyland, E. J., Lawton, C. L., and Blundell, J. E. (2007) Serotonergic drugs: effects on appetite expression and use for the treatment of obesity Drugs 67, 27-55
34. Gundlah, C., Martin, K. F., Heal, D. J., and Auerbach, S. B. (1997) In vivo criteria to differentiate monoamine reuptake inhibitors from releasing agents: sibutramine is a reuptake inhibitor J. Pharmacol. Exp. Ther. 283, 581-591
35. Tao, R., Fray, A., Aspley, S., Brammer, R., Heal, D., and Auerbach, S. (2002) Effects on serotonin in rat hypothalamus of D-fenfluramine, aminorex, phentermine and fluoxetine Eur. J. Pharmacol. 445, 69-81
36. Rothman, R. B. and Baumann, M. H. (2002) Serotonin releasing agents. Neurochemical, therapeutic and adverse effects Pharmacol., Biochem. Behav. 71, 825-836
37. 1C-receptors in drug-induced penile erections in rats Psychopharmacology 101, 57-61
38. 2C receptors mediate penile erections in rats: actions of novel and selective agonists and antagonists Eur. J. Pharmacol. 325, 9-12
39. 2 agonist Ro60 - 0175 and the indirect 5-HT agonist dexfenfluramine Br. J. Pharmacol. 133, 459-466
40. Grignaschi, G. and Samanin, R. (1992) Role of 5-HT receptors in the effect of d -fenfluramine on feeding patterns in the rat Eur. J. Pharmacol. 212, 287-289
41. 2C receptors in mediating fenfluramine-induced anorexia in rats Br. J. Pharmacol. 114, 373
42. 2C receptors Neuropharmacology 41, 200-209
43. Wong, D. T., Reid, L. R., and Threlkeld, P. G. (1988) Suppression of food intake in rats by fluoxetine: comparison of enantiomers and effects of serotonin antagonists Pharmacol., Biochem. Behav. 31, 475-479
44. Grignaschi, G. and Samanin, R. (1992) Role of serotonin and catecholamines in brain in the feeding suppressant effect of fluoxetine Neuropharmacology 31, 445-449
45. Grignaschi, G. and Samanin, R. (1993) Role of serotonin receptors in the effect of sertraline on feeding behaviour Psychopharmacology 110, 203-208
46. Lightowler, S., Wood, M., Brown, T., Glen, A., Blackburn, T., Tulloch, I., and Kennett, G. (1996) An investigation of the mechanism responsible for fluoxetine-induced hypophagia in rats Eur. J. Pharmacol. 296, 137-143
47. 2C receptors Br. J. Pharmacol. 124, 1781-1787
48. 2C receptors potentiates consequences of serotonin reuptake blockade Neuropsychopharmacology 29, 1782-1789
49. 2 receptor antagonists using in vivo microdialysis Neuropharmacology 50, 726-732
50. 2C receptors in CHO-K1 cells Br. J. Pharmacol. 128, 13-20
51. Berendsen, H. H. and Broekkamp, C. (1990) Behavioural evidence for functional interactions between 5-HT-receptor subtypes in rats and mice Br. J. Pharmacol. 101, 667-673
52. 2B receptors Behav. Pharmacol. 12, 613-620
53. 2C receptors exert opposing effects on locomotor activity in mice Neuropsychopharmacology 34, 1958-1967
54. 2C receptors in R (-)-2,5-dimethoxy-4-iodoamphetamine-elicited head twitch behavior in mice J. Pharmacol. Exp. Ther. 335, 728-734
55. 2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism Psychopharmacology. 170, 309-319
56. 2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion Psychopharmacology 176, 376-385
57. 2C receptor antagonists in the rat and mouse on premature responding in the five-choice serial reaction time test Psychopharmacology 195, 223-234
58. 2CR agonist suggests new pharmacotherapeutics for cocaine addiction ACS Chem. Neurosci. 4, 110-121
59. 2C receptor agonists Pharmacol., Biochem. Behav. 69, 643-652
60. 2C receptor antagonist Neuropharmacology 36, 609-620
61. 1C receptors in the behavioral effects of the 5-HT agonist 1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2 (DOI) Neurosci. Lett. 115, 74-80
62. Fone, K. C., Robinson, A. J., and Marsden, C. A. (1991) Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats Br. J. Pharmacol. 103, 1547-1555
63. 2C receptor antagonist SB242084 on locomotor activity induced by selective, or mixed, indirect serotonergic and dopaminergic agonists Psychopharmacology 187, 515-525
64. 2A receptors suppresses the induction of locomotor activity by 5-HT reuptake inhibitors, citalopram and fluvoxamine, in NMRI mice exposed to a novel environment: a comparison to other 5-HT receptor subtypes Psychopharmacology 168, 397-409
65. 2C receptor mutant mice J. Neurosci. 20, RC71
66. 2C receptor mutant mice is mediated by activation of multiple 5-HT receptor subtypes Neuropharmacology 46, 663-671
67. 2C receptor knockout mice Neuropharmacology 57, 259-267
68. Rothman, R. B., Blough, B. E., and Baumann, M. H. (2008) Dopamine/serotonin releasers as medications for stimulant addictions Prog. Brain Res. 172, 385-406
69. Connolly, H. M., Crary, J. L., McGoon, M. D., Hensrud, D. D., Edwards, B. S., Edwards, W. D., and Schaff, H. V. (1997) Valvular heart disease associated with fenfluramine-phentermine N. Engl. J. Med. 337, 581-588
70. Khan, M. A., Herzog, C. A., St. Peter, J. V., Hartley, G. G., Madlon-Kay, R., Dick, C. D., Asinger, R. W., and Vessey, J. T. (1998) The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs N. Engl. J. Med. 339, 713-718
71. Gardin, J. M., Schumacher, D., Constantine, G., Davis, K. D., Leung, C., and Reid, C. L. (2000) Valvular abnormalities and cardiovascular status following exposure to dexfenfluramine or phentermine/fenfluramine JAMA 283, 1703-1709
72. (1997) FDA Announces Withdrawal Fenfluramine and Dexfenfluramine, P97-32, U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER), Silver Spring, MD, http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm179871.htm.
73. Mast, S. T., Gersing, K. R., Anstrom, K. J., Krishnan, K. R., Califf, R. M., and Jollis, J. G. (2001) Association between selective serotonin-reuptake inhibitor therapy and heart valve regurgitation Am. J. Cardiol. 87, 989-993
74. Elangbam, C. S. (2010) Drug-induced valvulopathy: an update Toxicol. Pathol. 38, 837-848
75. 2B receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications Circulation 102, 2836-2841
76. 2B receptors in the cardiopathy associated with fenfluramine Mol. Pharmacol. 57, 75-81
77. Hutcheson, J. D., Setola, V., Roth, B. L., and Merryman, W. D. (2011) Serotonin receptors and heart valve disease-it was meant 2B Pharmacol. Ther. 132, 146-157
78. 2C) receptor agonists as potential anti-obesity agents J. Med. Chem. 49, 4023-4034
79. 2C receptor: preclinical and clinical progression in multiple diseases Curr. Opin. Drug Discovery Dev. 11, 438-445
80. 2C receptor modulators: a patent survey Expert Opin. Ther. Pat. 20, 1429-1455
81. 2C serotonin receptors Nature 374, 542-546
82. 2C receptor mutant mice Psychopharmacology 143, 309-314
83. 2C receptor agonists: pharmacological characteristics and therapeutic potential J. Pharmacol. Exp. Ther. 286, 913-924
84. Garfield, A. S. and Heisler, L. K. (2009) Pharmacological targeting of the serotonergic system for the treatment of obesity J. Physiol. 587, 49-60
85. 2C receptor agonist for the treatment of obesity J. Med. Chem. 51, 305-313
86. 2C agonist: in vitro and in vivo pharmacological characterization J. Pharmacol. Exp. Ther. 325, 577-587
87. 2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination and reinstatement: relationship to feeding behavior and impulse control Neuropsychopharmacology 37, 1177-1191
88. 2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of Diet-induced obesity Pharmacol. Res. Perspect. 3, e00084
89. 2C receptors tonically inhibit dopamine (DA) and noradrenaline (NA), but not 5-HT, release in the frontal cortex in vivo Neuropharmacology 37, 953-955
90. 2C receptor antagonist, increases dopaminergic transmission in the mesolimbic system Neuropharmacology 38, 1195-1205
91. 2B receptor agonists: a combined in vivo electrophysiological and microdialysis study Synapse 35, 53-61
92. 2C) receptors Brain Res. 865, 85-90
93. 2C receptors Neuroscience 103, 111-116
94. 2B receptor subtypes modulate dopamine release induced in vivo by amphetamine and morphine in both the rat nucleus accumbens and striatum Neuropsychopharmacology 26, 311-324
95. 2C receptors in the control of brain dopaminergic function Pharmacol., Biochem. Behav. 71, 727-734
96. 2C receptors on cocaine- and food-maintained behavior J. Pharmacol. Exp. Ther. 295, 1183-1191
97. 2C receptor agonist and d -fenfluramine on feeding patterns in the rat Psychopharmacology 152, 256-67
98. 2C receptor agonist Ro60-0175 reduces cocaine self-administration and reinstatement induced by the stressor yohimbine, and contextual cues Neuropsychopharmacology 33, 1402-1412
99. 2C receptor antagonist SB242084 on cocaine-induced locomotor activity, cocaine self-administration and cocaine-induced reinstatement of responding Neuropsychopharmacology 27, 576-586
100. 2C) receptors in rat prefrontal cortex J. Pharmacol. Exp. Ther. 306, 734-743
101. 2C receptor Behav. Neurosci. 118, 157-162
102. 2C receptor agonist Ro60-0175 into the ventral tegmental area reduces cocaine-induced locomotor activity and cocaine self-administration Neuropsychopharmacology 29, 308-318
103. 2C receptors attenuates cue and cocaine-primed reinstatement of cocaine-seeking behavior in rats Behav. Pharmacol. 18, 791-800
104. 2C receptors influences cocaine-seeking behavior in response to drug-associated stimuli in rats Psychopharmacology 196, 15-27
105. 2C receptors in the ventral tegmental area and the nucleus accumbens: an in vivo microdialysis study with cocaine Neuropsychopharmacology 33, 237-246
106. 2C) receptors attenuates cocaine-seeking behavior Neuropsychopharmacology 35, 2037-2048
107. 2C receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues Neuropharmacology 61, 513-523
108. 2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine Psychopharmacology 213, 337-354
109. Steed, E., Jones, C. A., and McCreary, A. C. (2011) Serotonergic involvement in methamphetamine-induced locomotor activity: a detailed pharmacological study Behav. Brain Res. 220, 9-19
110. 2C receptor agonists on the behavioral and neurochemical effects of cocaine in squirrel monkeys J. Pharmacol. Exp. Ther. 341, 424-434
111. 2C receptor antagonist SB 242084 exhibits abuse-related effects typical of stimulants in squirrel monkeys J. Pharmacol. Exp. Ther. 342, 761-769
112. 2C receptor function in amphetamine-induced 50-kHz ultrasonic vocalizations in rats Psychopharmacology 10.1007/s00213-014-3814-9
113. 2C agonist, shows activity in animal models of antipsychotic activity Neuropharmacology 52, 279-290
114. 2 receptor interactions with dopamine function: implications for therapeutics in cocaine use disorder Pharmacol. Rev. 67, 176-197
115. Matta, S. G., Balfour, D. J., Benowitz, N. L., Boyd, R. T., Buccafusco, J. J., Caggiula, A. R., Craig, C. R., Collins, A. C., Damaj, M. I., Donny, E. C., Gardiner, P. S., Grady, S. R., Heberlein, U., Leonard, S. S., Levin, E. D., Lukas, R. J., Markou, A., Marks, M. J., McCallum, S. E., Parameswaran, N., Perkins, K. A., Picciotto, M. R., Quik, M., Rose, J. E., Rothenfluh, A., Schafer, W. R., Stolerman, I. P., Tyndale, R. F., Wehner, J. M., and Zirger, J. M. (2007) Guidelines on nicotine dose selection for in vivo research Psychopharmacology 190, 269-319
116. Peto, R., Lopez, A. D., Boreham, J., Thun, M., Heath, C., Jr., and Doll, R. (1995) Mortality from smoking worldwide Br. Med. Bull. 52, 12-21
117. Wu, P., Wilson, K., Dimoulas, P., and Mills, E. J. (2006) Effectiveness of smoking cessation therapies: a systematic review and meta-analysis BMC Public Health 6, 300
118. Henningfield, J. E., Shiffman, S., Ferguson, S. G., and Gritz, E. R. (2009) Tobacco dependence and withdrawal: science base, challenges and opportunities for pharmacotherapy Pharmacol. Ther. 123, 1-16
119. Syed, B. A. and Chaudhari, K. (2013) Smoking cessation drugs market Nat. Rev. Drug Discovery 12, 97-98
120. 2C receptors reduces the locomotor and rewarding effects of nicotine Psychopharmacology 157, 292-298
121. Grottick, A. J., Wyler, R., and Higgins, G. A. (2000) The alpha4beta2 agonist SIB 1765F, but not the alpha7 agonist AR-R 17779, cross-sensitises to the psychostimulant effects of nicotine Psychopharmacology 150, 233-236
122. Tapper, A. R., McKinney, S. L., Nashmi, R., Schwarz, J., Deshpande, P., Labarca, C., Whiteaker, P., Marks, M. J., Collins, A. C., and Lester, H. A. (2004) Nicotine activation of alpha4∗ receptors: sufficient for reward, tolerance, and sensitization Science 306, 1029-1032
123. Zaniewska, M., McCreary, A. C., Stefański, R., Przegaliński, E., and Filip, M. (2008) Effect of varenicline on the acute and repeated locomotor responses to nicotine in rats Synapse 62, 935-939
124. Baker, L. K., Mao, D., Chi, H., Govind, A. P., Vallejo, Y. F., Iacoviello, M., Herrera, S., Cortright, J. J., Green, W. N., McGehee, D. S., and Vezina, P. (2013) Intermittent nicotine exposure upregulates nAChRs in VTA dopamine neurons and sensitises locomotor responding to the drug Eur. J. Neurosci. 37, 1004-1011
125. 2C receptors blocks the hyperactivation of midbrain dopamine neurons induced by nicotine administration J. Pharmacol. Exp. Ther. 309, 109-118
126. 2C receptors blocks the enhancement of striatal and accumbal dopamine release induced by nicotine administration J. Neurochem. 89, 418-429
127. Corrigall, W. A., Coen, K. M., and Adamson, K. L. (1994) Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area Brain Res. 653, 278-284
128. Maskos, U., Molles, B. E., Pons, S., Besson, M., Guiard, B. P., Guilloux, J. P., Evrard, A., Cazala, P., Cormier, A., Mameli-Engvall, M., Dufour, N., Cloëz-Tayarani, I., Bemelmans, A. P., Mallet, J., Gardier, A. M., David, V., Faure, P., Granon, S., and Changeux, J. P. (2005) Nicotine reinforcement and cognition restored by targeted expression of nicotinic receptors Nature 436, 103-107
129. Keath, J. R., Iacoviello, M. P., Barrett, L. E., Mansvelder, H. D., and McGehee, D. S. (2007) Differential modulation by nicotine of substantia nigra versus ventral tegmental area dopamine neurons J. Neurophysiol. 98, 3388-3396
130. McGranahan, T. M., Patzlaff, N. E., Grady, S. R., Heinemann, S. F., and Booker, T. K. (2011) α4β2 nicotinic acetylcholine receptors on dopaminergic neurons mediate nicotine reward and anxiety relief J. Neurosci. 31, 10891-10902
131. 2C receptor agonist Ro 60-0175 and the 5-HT2A receptor antagonist M100907 on nicotine self-administration and reinstatement Neuropharmacology 62, 2287-2297
132. Ussher, M., Beard, E., Abikoye, G., Hajek, P., and West, R. (2013) Urge to smoke over 52 weeks of abstinence Psychopharmacology 226, 83-89
133. 2C receptor agonist Ro-60-0175 attenuates effects of nicotine in the five-choice serial reaction time task and in drug discrimination Psychopharmacology 193, 391-402
134. 2C receptor ligands on the discriminative stimulus effects of nicotine in rats Eur. J. Pharmacol. 571, 156-165
135. 2C receptor agonists on behaviours motivated by food and nicotine and on side effect profiles Psychopharmacology 226, 475-490
136. 2C agonist, decreases nicotine self-administration in female rats J. Pharmacol. Exp. Ther. 338, 890-896
137. Guy, E. G., Fisher, D. C., Higgins, G. A., and Fletcher, P. J. (2014) Examination of the effects of varenicline, bupropion, lorcaserin, or naltrexone on responding for conditioned reinforcement in nicotine-exposed rats Behav. Pharmacol. 25, 775-783
138. Chaudhri, N., Caggiula, A. R., Donny, E. C., Palmatier, M. I., Liu, X., and Sved, A. F. (2006) Complex interactions between nicotine and non-pharmacological stimuli reveal multiple roles for nicotine in reinforcement Psychopharmacology 184, 353-66
139. Zeeb, F. D., Higgins, G. A., and Fletcher, P. J. (2015) The serotonin 2C receptor agonist Lorcaserin attenuates intracranial self-stimulation and blocks the reward-enhancing effects of nicotine ACS Chem. Neurosci. 10.1021/acschemneuro.5b00017
140. (2010) FDA Briefing Document NDA 22529, Lorcaserin hydrochloride (APD356), Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, MD.
141. 2C agonist, reduces body weight in obese men and women Obesity 17, 494-503
142. Smith, S. R., Weissman, N. J., Anderson, C. M., Sanchez, M., Chuang, E., Stubbe, S., Bays, H., Shanahan, W. R., and Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group (2010) Multicentre, placebo-controlled trial of lorcaserin for weight management N. Engl. J. Med. 263, 245-256
143. Fidler, M. C., Sanchez, M., Raether, B., Weissman, N. J., Smith, S. R., Shanahan, W. R., and Anderson, C. M. (2011) A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial J. Clin. Endocrinol. Metab. 96, 3067-3077
144. O'Neil, P. M., Smith, S. R., Weissman, N. J., Fidler, M. C., Sanchez, M., Zhang, J., Raether, B., Anderson, C. M., and Shanahan, W. R. (2012) Randomized placebo-controlled clinical trial of lorcaserin for weight loss in type 2 diabetes mellitus: the BLOOM-DM study Obesity 20, 1426-1436
145. Malin, D. H. (2001) Nicotine dependence: studies with a laboratory model Pharmacol., Biochem. Behav. 70, 551-559
146. Malin, D. H. and Goyarzu, P. (2009) Rodent models of nicotine withdrawal syndrome Handb. Exp. Pharmacol. 192, 401-434
147. Barnes, N. M. and Sharp, T. (1999) A review of central 5-HT receptors and their function Neuropharmacology 38, 1083-1152
148. 2 receptor ligands on depression-like behavior during nicotine withdrawal Neuropharmacology 58, 1140-1146
149. Hall, S. M., Muñoz, R. F., Reus, V. I., and Sees, K. L. (1993) Nicotine, negative affect, and depression J. Consult. Clin. Psychol. 61, 761-767
150. Benowitz, N. L. (2008) Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction Clin. Pharmacol. Ther. 83, 531-541
151. Jackson, K. J., Muldoon, P. P., De Biasi, M., and Damaj, M. I. (2014) New mechanisms and perspectives in nicotine withdrawal Neuropharmacology 10.1016/j.neuropharm.2014.11.009
152. Volkow, N. D. and Wise, R. A. (2005) How can drug addiction help us understand obesity? Nat. Neurosci. 8, 555-560
153. Kenny, P. J. (2011) Reward mechanisms in obesity: new insights and future directions Neuron 69, 664-679
154. Barry, D., Clarke, M., and Petry, N. M. (2009) Obesity and its relationship to addictions: is overeating a form of addictive behavior? Am. J. Addict. 18, 439-451
155. Hoebel, B. G., Avena, N. M., Bocarsly, M. E., and Rada, P. (2009) Natural addiction: a behavioral and circuit model based on sugar addiction in rats J. Addict. Med. 3, 33-41
156. Parylak, S. L., Koob, G. F., and Zorrilla, E. P. (2011) The dark side of food addiction Physiol. Behav. 104, 149-156
157. Volkow, N. D. and O'Brien, C. P. (2007) Issues for DSM-V: should obesity be included as a brain disorder? Am. J. Psychiatry 164, 708-710
158. Evenden, J. L. (1999) Varieties of impulsivity Psychopharmacology 146, 348-361
159. Winstanley, C. A., Olausson, P., Taylor, J. R., and Jentsch, J. D. (2010) Insight into the relationship between impulsivity and substance abuse from studies using animal models Alcohol.: Clin. Exp. Res. 34, 1306-1318
160. Bari, A. and Robbins, T. W. (2013) Inhibition and impulsivity: behavioral and neural basis of response control Prog. Neurobiol. 108, 44-79
161. Winstanley, C. A. (2011) The utility of rat models of impulsivity in developing pharmacotherapies for impulse control disorders Br. J. Pharmacol. 164, 1301-1321
162. Dalley, J. W., Everitt, B. J., and Robbins, T. W. (2011) Impulsivity, compulsivity, and top-down cognitive control Neuron 69, 680-694
163. Soubrie, P. (1986) Reconciling the role of central serotonin neurons in human and animal behavior Behav. Brain Sci. 9, 319-364
164. Harrison, A. A., Everitt, B. J., and Robbins, T. W. (1997) Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms Psychopharmacology 133, 329-342
165. 1A receptor agonist 8-OH-DPAT reduces rats' accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT(1A) receptors Psychopharmacology 149, 259-268
166. Winstanley, C. A., Dalley, J. W., Theobald, D. E., and Robbins, T. W. (2004) Fractionating impulsivity: contrasting effects of central 5-HT depletion on different measures of impulsive behavior Neuropsychopharmacology 29, 1331-1343
167. Wogar, M. A., Bradshaw, C. M., and Szabadi, E. (1992) Impaired acquisition of temporal differentiation performance following lesions of the ascending 5-hydroxytryptaminergic pathways Psychopharmacology 107, 373-378
168. Wogar, M. A., Bradshaw, C. M., and Szabadi, E. (1993) Does the effect of central 5-hydroxytryptamine depletion on timing depend on motivational change? Psychopharmacology 112, 86-92
169. Fletcher, P. J. (1995) Effects of combined or separate 5,7-dihydroxytryptamine lesions of the dorsal and median raphe nuclei on responding maintained by a DRL 20s schedule of food reinforcement Brain Res. 675, 45-54
170. Paterson, N. E., Wetzler, C., Hackett, A., and Hanania, T. (2012) Impulsive action and impulsive choice are mediated by distinct neuropharmacological substrates in rat Int. J. Neuropsychopharmacol. 15, 1473-1487
171. Wogar, M. A., Bradshaw, C. M., and Szabadi, E. (1993) Effect of lesions of the ascending 5-hydroxytryptaminergic pathways on choice between delayed reinforcers Psychopharmacology 111, 239-243
172. Mobini, S., Chiang, T. J., Al-Ruwaitea, A. S., Ho, M. Y., Bradshaw, C. M., and Szabadi, E. (2000) Effect of central 5-hydroxytryptamine depletion on inter-temporal choice: a quantitative analysis Psychopharmacology 149, 313-318
173. Broos, N., Schmaal, L., Wiskerke, J., Kostelijk, L., Lam, T., Stoop, N., Weierink, L., Ham, J., de Geus, E. J., Schoffelmeer, A. N., van den Brink, W., Veltman, D. J., de Vries, T. J., Pattij, T., and Goudriaan, A. E. (2012) The relationship between impulsive choice and impulsive action: a cross-species translational study PLoS One 7, e36781
174. Worbe, Y., Savulich, G., Voon, V., Fernandez-Egea, E., and Robbins, T. W. (2014) Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance Neuropsychopharmacology 239, 1519-1526
175. Pattij, T. and De Vries, T. J. (2013) The role of impulsivity in relapse vulnerability Curr. Opin. Neurobiol. 23, 700-705
176. Dalley, J. W., Fryer, T. D., Brichard, L., Robinson, E. S., Theobald, D. E., Lääne, K., Peña, Y., Murphy, E. R., Shah, Y., Probst, K., Abakumova, I., Aigbirhio, F. I., Richards, H. K., Hong, Y., Baron, J. C., Everitt, B. J., and Robbins, T. W. (2007) Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement Science 315, 1267-1270
177. Perry, J. L., Nelson, S. E., and Carroll, M. E. (2008) Impulsive choice as a predictor of acquisition of IV cocaine self- administration and reinstatement of cocaine-seeking behavior in male and female rats Exp. Clin. Psychopharmacol. 16, 165-177
178. Zlebnik, N. E. and Carroll, M. E. (2015) Effects of the combination of wheel running and atomoxetine on cue- and cocaine-primed reinstatement in rats selected for high or low impulsivity Psychopharmacology 232, 1049-1059
179. Diergaarde, L., Pattij, T., Poortvleit, I., Hogenboom, F., de Vries, W., Schoffelmeer, A. N. M., and De Vries, T. J. (2008) Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats Biol. Psychiatry 63, 301-308
180. Velázquez-Sánchez, C., Ferragud, A., Moore, C. F., Everitt, B. J., Sabino, V., and Cottone, P. (2014) High trait impulsivity predicts food addiction-like behavior in the rat Neuropsychopharmacology 39, 2463-2472
181. Koob, G. F., Rocio, M., Carrera, A., Gold, L. H., Heyser, C. J., Maldonado-Irizarry, C., Markou, A., Parsons, L. H., Roberts, A. J., Schulteis, G., Stinus, L., Walker, J. R., Weissenborn, R., and Weiss, F. (1998) Substance dependence as a compulsive behavior J. Psychopharmacol. 12, 39-48
182. Ahmed, S. H. and Koob, G. F. (1998) Transition from moderate to excessive drug intake: change in hedonic set point Science 282, 298-300
183. Vanderschuren, L. J. and Everitt, B. J. (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration Science 305, 1017-1019
184. Everitt, B. J. and Robbins, T. W. (2005) Neural systems of reinforcement for drug addiction: from actions to habits to compulsion Nat. Neurosci. 8, 1481-1489
185. Belin, D., Mar, A. C., Dalley, J. W., Robbins, T. W., and Everitt, B. J. (2008) High impulsivity predicts the switch to compulsive cocaine-taking Science 320, 1352-1355
186. Pelloux, Y., Dilleen, R., Economidou, D., Theobald, D., and Everitt, B. J. (2012) Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats Neuropsychopharmacology 37, 2505-2514
187. Economidou, D., Pelloux, Y., Robbins, T. W., Dalley, J. W., and Everitt, B. J. (2009) High impulsivity predicts relapse to cocaine-seeking after punishment-induced abstinence Biol. Psychiatry 65, 851-856
188. Broos, N., Diergaarde, L., Schoffelmeer, A. N., Pattij, T., and De Vries, T. J. (2012) Trait impulsive choice predicts resistance to extinction and propensity to relapse to cocaine seeking: a bidirectional investigation Neuropsychopharmacology 37, 1377-1386
189. 2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence Neuropsychopharmacology 39, 370-382
190. 2C receptor system aligns with vulnerability to cocaine cue reactivity Transl. Psychiatry 4, e369
191. 2C receptor antagonist, SB-242084, in tests of anxiety Pharmacol., Biochem. Behav. 71, 615-625
192. 2C) receptor agonist WAY-163909 decreases impulsivity in the 5-choice serial reaction time test Behav. Brain Res. 188, 412-415
193. Shaham, Y., Shalev, U., Lu, L., De Wit, H., and Stewart, J. (2003) The reinstatement model of drug relapse: history, methodology and major findings Psychopharmacology 168, 3-20
194. Bossert, J. M., Marchant, N. J., Calu, D. J., and Shaham, Y. (2013) The reinstatement model of drug relapse: recent neurobiological findings, emerging research topics, and translational research Psychopharmacology 229, 453-476
195. Epstein, D. H., Preston, K. L., Stewart, J., and Shaham, Y. (2006) Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure Psychopharmacology 189, 1-16
196. Rose, J. E. and Levin, E. D. (1991) Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking Br. J. Addict. 86, 605-609
197. Chudasama, Y., Passetti, F., Rhodes, S. E., Lopian, D., Desai, A., and Robbins, T. W. (2003) Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity Behav. Brain Res. 146, 105-119
198. Carli, M. and Invernizzi, R. W. (2014) Serotoninergic and dopaminergic modulation of cortico-striatal circuit in executive and attention deficits induced by NMDA receptor hypofunction in the 5-choice serial reaction time task Front. Neural Circuits 8, 58
199. (2012) FDA Approves Belviq To Treat Some Overweight or Obese Adults, http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm309993.htm.
200. Aronne, L., Shanahan, W., Fain, R., Glicklich, A., Soliman, W., Li, Y., and Smith, S. (2014) Safety and efficacy of lorcaserin: a combined analysis of the BLOOM and BLOSSOM trials Postgrad. Med. 126, 7-18
201. Weissman, N. J., Sanchez, M., Koch, G. G., Smith, S. R., Shanahan, W. R., and Anderson, C. M. (2013) Echocardiographic assessment of cardiac valvular regurgitation with lorcaserin from analysis of 3 phase 3 clinical trials Circ. Cardiovasc. Imaging 6, 560-567
202. 2C) receptor agonist, in recreational polydrug users Clin. Pharmacol. Ther. 89, 683-692
203. (2013) Schedules of Controlled Substances: Placement of lorcaserin into Schedule IV, DEA, https://www.federalregister.gov/articles/2013/05/08/2013-10895/schedules-of-controlled-substances-placement-of-lorcaserin-into-schedule-iv.
204. A Study To Evaluate the Effect of Lorcaserin Hydrochloride on Smoking Cessation, https://clinicaltrials.gov/ct2/show/study/NCT02044874.
205. Lorcaserin Meets Primary Endpoint and Confirms Proof-of-Concept as Potential Aid for Smoking Cessation in Investigational Phase II Study, http://www.eisai.com/news/enews201465pdf.pdf.
206. 2C receptor agonist J. Pharmacol. Exp. Ther. 337, 673-680
207. 2C agonists as therapeutics for the treatment of schizophrenia Handb. Exp. Pharmacol. 213, 147-165
208. Shen, J. H., Zhao, Y., Rosenzweig-Lipson, S., Popp, D., Williams, J. B., Giller, E., Detke, M. J., and Kane, J. M. (2014) A 6-week randomized, double-blind, placebo-controlled, comparator referenced trial of vabicaserin in acute schizophrenia J. Psychiatr. Res. 53, 14-22
209. 2C agonist, for the treatment of schizophrenia using a quantitative systems pharmacology model CPT: Pharmacometrics Syst. Pharmacol. 3, e111
210. Blundell, J. E., Levin, F., King, N. A., Barkeling, B., Gustafsson, T., Hellstrom, P. M., Holst, J. J., and Naslund, E. (2008) Overconsumption and obesity: peptides and susceptibility to weight gain Regul. Pept. 149, 32-38
211. Berthoud, H.-R. (2011) Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr. Opin. Neurobiol. 21, 888-896
212. Harrold, J. A., Dovey, T. M., Blundell, J. E., and Halford, J. C. (2012) CNS regulation of appetite Neuropharmacology 63, 3-17
213. Smith, D. G. and Robbins, T. W. (2013) The neurobiological underpinnings of obesity and binge eating: a rationale for adopting the food addiction model Biol. Psychiatry 73, 804-810
214. Schag, K., Teufel, M., Junne, F., Preissl, H., Hautzinger, M., Zipfel, S., and Giel, K. E. (2013) Impulsivity in binge eating disorder: food cues elicit increased reward responses and disinhibition PLoS One 8 e76542
215. 2C receptor agonist promotes hypophagia via downstream activation of melanocortin 4 receptors Endocrinology 149, 1323-1328
216. Avena, N. M. (2010) The study of food addiction using animal models of binge eating Appetite 55, 734-737
217. Corwin, R. L., Avena, N. M., and Boggiano, M. M. (2011) Feeding and reward: perspectives from three rat models of binge eating Physiol. Behav. 104, 87-97
218. Furlong, T. M., Jayaweera, H. K., Balleine, B. W., and Corbit, L. H. (2014) Binge-like consumption of a palatable food accelerates habitual control of behavior and is dependent on activation of the dorsolateral striatum J. Neurosci. 34, 5012-5022
219. 2C receptors in modifying ethanol self-administration behaviour Pharmacol., Biochem. Behav. 71, 735-744
220. 2C receptors to alter drug abuse and dependence processes Brain Res. 1476, 132-153
221. 2C receptor agonists Trends Pharmacol. Sci. 34, 560-570
222. Kasper, J., Tikamdas, R., Kim, M. S., Macfadyen, K., Aramini, R., Ladd, J., Bisceglia, S., Booth, R., and Peris, J. (2013) The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol consumption in rats Eur. J. Pharmacol. 718, 98-104
223. 2C receptor agonist, decreases alcohol intake in female alcohol preferring rats Pharmacol., Biochem. Behav. 125, 8-14
224. Robinson, E. S., Eagle, D. M., Mar, A. C., Bari, A., Banerjee, G., Jiang, X., Dalley, J. W., and Robbins, T. W. (2008) Similar effects of the selective noradrenaline reuptake inhibitor atomoxetine on three distinct forms of impulsivity in the rat Neuropsychopharmacology 33, 1028-1037
225. Robinson, E. S. (2012) Blockade of noradrenaline re-uptake sites improves accuracy and impulse control in rats performing a five-choice serial reaction time tasks Psychopharmacology 219, 303-312
226. Baarendse, P. J. and Vanderschuren, L. J. (2012) Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats Psychopharmacology 219, 313-326
227. Economidou, D., Dalley, J. W., and Everitt, B. J. (2011) Selective norepinephrine reuptake inhibition by atomoxetine prevents cue-induced heroin and cocaine seeking Biol. Psychiatry 69, 266-274
228. Broos, N., Loonstra, R., van Mourik, Y., Schetter, D., Schoffelmeer, A. N., Pattij, T., and De Vries, T. J. (2015) Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making Addict. Biol. 10.1111/adb.12168.
229. (2012) Lorcaserin: Receptor Pharmacology and Selectivity NDA 22-529 CR Resubmission, U.S. Food and Drug Administration Center for Drug Evaluation and Research (CDER), Silver Spring, MD, http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM305376.pdf.
230. 2C receptors ACS Chem. Neurosci. 4, 261-265
231. Christopoulos, A. (2002) Allosteric binding sites on cell-surface receptors: novel targets for drug discovery Nat. Rev. Drug Discovery 1, 198-210
232. Conn, P. J., Christopoulos, A., and Lindsley, C. W. (2009) Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders Nat. Rev. Drug Discovery 8, 41-54
233. 2C receptor Mol. Pharmacol. 64, 78-84
234. 2C receptor allosteric modulators ACS Chem. Neurosci. 3, 538-545
235. Urban, J. D., Clarke, W. P., von Zastrow, M., Nichols, D. E., Kobilka, B., Weinstein, H., Javitch, J. A., Roth, B. L., Christopoulos, A., Sexton, P. M., Miller, K. J., Spedding, M., and Mailman, R. B. (2007) Functional selectivity and classical concepts of quantitative pharmacology J. Pharmacol. Exp. Ther. 320, 1-13
236. Hannon, J. and Hoyer, D. (2008) Molecular biology of 5-HT receptors Behav. Brain Res. 195, 198-213
237. Berg, K. A., Maayani, S., Goldfarb, J., Scaramellini, C., Leff, P., and Clarke, W. P. (1998) Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus Mol. Pharmacol. 54, 94-104
238. 2C receptor ligands and the 2,5-dimethoxy-4-iodoamphetamine elicited head-twitch response model Neuropharmacology 70, 112-121
239. Berg, K. A. and Clarke, W. P. (2005) Development of functionally selective agonists as novel therapeutic agents Drug Discovery Today: Ther. Strategies 3, 421-428
240. Mailman, R. B. (2007) GPCR functional selectivity has therapeutic impact Trends Pharmacol. Sci. 28, 390-396
241. 2C receptor activation interact to reduce cocaine hyperlocomotion and Fos protein expression in the caudate-putamen Synapse 66, 989-1001
242. 2B receptor inverse agonist/antagonist activity Eur. J. Pharmacol. 615, 1-9
243. 2 modulators: potential utility as antipsychotic medications Neuropharmacology 72, 274-281
244. 2B inverse agonist with preclinical efficacy for psychoses J. Pharmacol. Exp. Ther. 349, 310-318
245. Grottick, A. J. and Higgins, G. A. (2000) Effect of subtype selective nicotinic compounds on attention as assessed by the five-choice serial reaction time task Behav. Brain Res. 117, 197-208
246. Abramowski, D., Rigo, M., Duc, D., Hoyer, D., and Staufenbiel, M. (1995) Localization of the 5-hydroxytryptamine2C receptor protein in human and rat brain using specific antisera Neuropharmacology 34, 1635-1645
247. 3H]mesulergine binding in human brain postmortem Eur. Neuropsychopharmacol. 10, 21-26
248. 3H]mesulergine binding sites and choline acetyltransferase mRNA Synapse 42, 12-26