Elevated expression of serotonin 5-HT2A receptors in the rat ventral tegmental area enhances vulnerability to the behavioral effects of cocaine

Frontiers in Psychiatry

Volumn 4, Issue FEB, 2013, Pages

  Herin, David V ^a   Bubar, Marcy J ^a   Seitz, Patricia K ^a   Thomas, Mary L ^a,b   Hillman, Gilbert R ^a   Tarasenko, Yevgeniya I ^a   Wu, Ping ^a   Cunningham, Kathryn A ^a  

^a University of Texas Medical Branch School of Medicine   (United States)

^b ROSS UNIVERSITY SCHOOL OF MEDICINE   (Dominica)

Author keywords

5 HT2A receptor; AAV; Cocaine; Locomotor activity; Psychostimulants; Serotonin; Ventral tegmental area; Virally mediated gene transfer

Indexed keywords

ADENOVIRUS VECTOR; COCAINE; FLAG PROTEIN; PLASMID DNA; SEROTONIN 2A RECEPTOR; SYNTHETIC PEPTIDE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIBODY LABELING; ARTICLE; BRAIN REGION; CONTROLLED STUDY; DRUG ADMINISTRATION ROUTE; EVOKED RESPONSE; HEMISPHERE; HYPERACTIVITY; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; INTRAVENTRAL TEGMENTAL AREA ADMINISTRATION; LOCOMOTION; MALE; NERVE CELL; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; RAT; REGULATORY MECHANISM; VENTRAL TEGMENTUM; VIRAL GENE DELIVERY SYSTEM; VIRUS RECOMBINANT;

EID: 84877705345     PISSN: None     EISSN: 16640640     Source Type: Journal    
DOI: 10.3389/fpsyt.2013.00002     Document Type: Article

References (91)

1. Alex, K. D., and Pehek, E. A. (2007). Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol. Ther. 113, 296-320.
2. Allen, A. R., and MacPhail, R. C. (1991). Effects of triadimefon on a multiple schedule of fixed-interval performance: comparison with methylphenidate, d-amphetamine and chlorpromazine. Pharmacol. Biochem. Behav. 40, 775-780.
3. Anastasio, N. C., Gilbertson, S. R., Bubar, M. J., Agarkov, A., Stutz, S. J., Jeng, Y. J., et al. (2013). Peptide inhibitors disrupt the serotonin 5-HT2C receptor interaction with phosphatase and tensin homologue (PTEN) to allosterically modulate cellular signaling and behavior. J. Neurosci. 33, 1615-1630.
4. Anastasio,N. C.,Stoffel,E. C.,Fox,R. G., Bubar, M. J., Rice, K. C., and Moeller, F. G., et al. (2011). Serotonin (5hydroxytryptamine) 5-HT2A receptor: Association with inherent and cocaine-evoked behavioral disinhibition in rats. Behav. Pharmacol. 22, 248-261.
5. Auclair, A., Blanc, G., Glowinski, J., and Tassin, J. P. (2004). Role of serotonin 2A receptors in the D-amphetamine-induced release of dopamine: comparison with previous data on alpha1b-adrenergic receptors. J. Neurochem. 91, 318-326.
6. Berg, K. A., Clarke, W. P., Chen, Y., Ebersole, B. J., McKay, R. D. G., and Maayani, S. (1994). 5hydroxytryptamine type 2A receptors regulate cyclic AMP accumulation in a neuronal cell line by protein kinase C-dependent and calcium/calmodulin-dependent mechanisms. Mol. Pharmacol. 45, 826-836.
7. Berg, K. A., Harvey, J. A., Spampinato, U., and Clarke, W. P. (2005). Physiological relevance of constitutive activity of 5-HT2A and 5-HT2C receptors. Trends Pharmacol. Sci. 26, 625-630.
8. Bolanos, C. A., Perrotti, L. I., Edwards, S., Eisch,A. J., Barrot, M., and Olson, V. G., et al. (2003). Phospholipase Cgamma in distinct regions of the ventral tegmental area differentially modulates mood-related behaviors. J. Neurosci. 23, 7569-7576.
9. Bonaccorso,S.,Meltzer,H.Y.,Li,Z.,Dai, J., Alboszta, A. R., and Ichikawa, J. (2002). SR46349-B, a 5-HT(2A/2C) receptor antagonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Neuropsychopharmacology 27, 430-441.
10. Broderick, P. A., Olabisi, O. A., Rahni, D. N., and Zhou, Y. (2004). Cocaine acts on accumbens monoamines and locomotor behavior via a 5-HT2A/2C receptor mechanism as shown by ketanserin: 24-h follow-up studies. Prog. Neuropsychopharmacol. Biol. Psychiatry 28, 547-557.
11. Browning, J. L., Patel, T., Brandt, P. C., Young, K. A., Holcomb, L. A., and Hicks, P. B. (2005). Clozapine and the mitogen-activated protein kinase signal transduction pathway: implications for antipsychotic actions. Biol. Psychiatry 57, 617-623.
12. Bubar, M. J., and Cunningham, K. A. (2007). Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience 146, 286-277.
13. Bubar, M. J., and Cunningham, K. A. (2008). Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. Prog. Brain Res. 172, 319-346.
14. Bubar, M. J., McMahon, L. R., De Deurwaerdere, P., Spampinato, U., and Cunningham, K. A. (2003). Selective serotonin reuptake inhibitors enhance cocaine-induced locomotor activity and dopamine release in the nucleus accumbens. Neuropharmacology 44, 342-353.
15. Bubar, M. J., Seitz, P. K., Thomas, M. L., and Cunningham, K. A. (2005). Validation of a selective serotonin 5-HT(2C) receptor antibody for utilization in fluorescence immunohistochemistry studies. Brain Res. 1063, 105-113.
16. Bubar, M. J., Stutz, S. J., and Cunningham, K. A. (2011). 5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway. PLoS ONE 6:e20508. doi:10.1371/journal.pone.0020508
17. Callahan, P. M., De La Garza, R., and Cunningham, K. A. (1994). Discriminative stimulus properties of cocaine: Modification by dopamine D1 receptors in nucleus accumbens. Psychopharmacology (Berl.) 115, 110-114.
18. Carlezon, W. A. Jr., Boundy,V. A., Haile, C. N., Lane, S. B., Kalb, R. G., and Neve, R. L., et al. (1997). Sensitization to morphine induced by viralmediated gene transfer. Science 277, 812-814.
19. Chamberlin, N. L., Du, B., de, L. S., and Saper, C. B. (1998). Recombinant adeno-associated virus vector: use for transgene expression and anterograde tract tracing in the CNS. Brain Res. 793, 169-175.
20. Chen, N.-H., and Reith, M. E. A. (1994). Effects of locally applied cocaine, lidocaine, and various uptake blockers on monoamine transmission in the ventral tegmental area of freely moving rats: a microdialysis study on monoamine interrelationships. J. Neurochem. 63, 1701-1713.
21. Cornea-Hebert, V., Riad, M., Wu, C., Singh, S. K., and Descarries, L. (1999). Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat. J. Comp. Neurol. 409, 187-209.
22. Cornea-Hebert,V.,Watkins,K. C.,Roth, B. L., Kroeze, W. K., Gaudreau, P., and Leclerc, N., et al. (2002). Similar ultrastructural distribution of the 5-HT(2A) serotonin receptor and microtubule-associated protein MAP1A in cortical dendrites of adult rat. Neuroscience 113, 23-35.
23. Couzin, J. (2006). Scientific publishing. Don't pretty up that picture just yet. Science 314, 1866-1868.
24. Cunningham, K. A., Anastasio, N. C., Fox, R. G., Stutz, S. J., Bubar, M. J., and Swinford, S. E., et al. (2013). Synergism between a serotonin 5HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction. ACS Chem. Neurosci. 4, 110-121.
25. De Deurwaerdere, P., and Spampinato, U. (1999). Role of serotonin(2A) and serotonin(2B/2C) receptor subtypes in the control of accumbal and striatal dopamine release elicited in vivo by dorsal raphe nucleus electrical stimulation. J. Neurochem. 73, 1033-1042.
26. De La Garza, R., and Cunningham, K. A. (2000). The effects of the 5-HT1A agonist 8-hydroxy-2(din-propylamino)tetralin on spontaneous activity and cocaine-induced hyperactivity and behavioral sensitization. J. Pharmacol. Exp. Ther. 292, 610-617.
27. Delfs, J. M., Schreiber, L., and Kelley, A. E. (1990). Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat. J. Neurosci. 10, 303-310.
28. Di Giovanni, G., De Deurwaerdere, P., Di Mascio, M., Di Matteo, V., Esposito, E., and Spampinato, U. (1999). Selective blockade of serotonin2C/2B receptors enhances mesolimbic and mesostriatal dopaminergic function: a combined in vivo electrophysiological and microdialysis study. Neuroscience 91, 587-597.
29. Doherty, M. D., and Pickel, V. M. (2000). Ultrastructural localization of the 5-HT2A receptor in dopaminergic neurons in the ventral tegmental area. Brain Res. 864, 176-185.
30. Edry, E., Lamprecht, R., Wagner, S., and Rosenblum, K. (2011). Virally mediated gene manipulation in the adult CNS. Front. Mol. Neurosci. 4:57. doi:10.3389/fnmol.2011.00057
31. Ehrengruber, M. U., Hennou, S., Bueler, H., Naim, H. Y., Deglon, N., and Lundstrom, K. (2001). Gene transfer into neurons from hippocampal slices: comparison of recombinant Semliki forest virus, adenovirus, adeno-associated virus, lentivirus, and measles virus. Mol. Cell Neurosci. 17, 855-871.
32. Filip, M., Alenina, N., Bader, M., and Przegalinski, E. (2010). Behavioral evidence for the significance of serotoninergic (5-HT) receptors in cocaine addiction. Addict. Biol. 15, 227-249.
33. Filip,M.,Bubar,M.J.,andCunningham, K. A. (2004). Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses. J. Pharmacol. Exp. Ther. 310, 1246-1254.
34. Filip,M.,Bubar,M. J.,andCunningham, K. A. (2006). Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats. Psychopharmacology (Berl.) 183, 482-489.
35. Filip, M., and Cunningham, K. A. (2002). Serotonin 5-HT(2C) receptors in nucleus accumbens regulate expression of the hyperlocomotive and discriminative stimulus effects of cocaine. Pharmacol. Biochem. Behav. 71, 745-756.
36. Fletcher, P. J., Grottick, A. J., and Higgins,G.A. (2002). Differential effects of the 5-HT2A receptor antagonist M100,907 and the 5-HT2C receptor antagonist SB242,084 on cocaine-induced locomotor activity, cocaine self-administration and cocaine-induced reinstatement of responding. Neuropsychopharmacology 27, 576-586.
37. Fletcher, P. J., Rizos, Z., Noble, K., and Higgins, G. A. (2011). Impulsive action induced by amphetamine,cocaine and MK801 is reduced by 5-HT(2C) receptor stimulation and 5-HT(2A) receptor blockade. Neuropharmacology 61, 468-477.
38. Garlow, S. J., Morilak, D. A., Dean, R. R., Roth, B. L., and Ciaranello, R. D. (1993). Production and characterization of a specific 5-HT2 receptor antibody. Brain Res. 615, 113-120.
39. Halliday, G. M., and Tork, I. (1989). Serotonin-Like immunoreactive cells and fibres in the rat ventromedial mesencephalic tegmentum. Brain Res. Bull. 22, 725-735.
40. Herges, S., and Taylor, D. A. (1998). Involvement of serotonin in the modulation of cocaine-induced locomotor activity in the rat. Pharmacol. Biochem. Behav. 59, 595-611.
41. Herin, D. V., Liu, S., Ullrich, T., Rice, K. C., and Cunningham, K. A. (2005). Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4methylenedioxymethamphetamine. Psychopharmacology (Berl.) 178, 505-513.
42. Hillman, G. (1984). Quantitation of acetylcholinesterase in frozen tissue sections by computer image analysis. Pharmacologist 26, 225.
43. Hoyer, D., Hannon, J. P., and Martin, G. R. (2002). Molecular, pharmacological and functional diversity of 5HT receptors. Pharmacol. Biochem. Behav. 71, 533-554.
44. Ikemoto, K., Nishimura, A., Okado, N., Mikuni, M., Nishi, K., and Nagatsu, I. (2000). Human midbrain dopamine neurons express serotonin 2A receptor: an immunohistochemical demonstration. Brain Res. 853, 377-380.
45. Ikemoto, S. (2007). Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex. Brain Res. Rev. 56, 27-78.
46. Jansson, A., Tinner, B., Bancila, M., Verge, D., Steinbusch, H. W., and Agnati, L. F., et al. (2001). Relationships of 5-hydroxytryptamine immunoreactive terminal-like varicosities to 5-hydroxytryptamine-2A receptor-immunoreactive neuronal processes in the rat forebrain. J. Chem. Neuroanat. 22, 185-203.
47. Johnson, S. W., and North, R. A. (1992). Two types of neurone in the rat ventral tegmental area and their synaptic inputs. J. Physiol. (Lond.) 450, 455-468.
48. Kaplitt,M. G.,Feigin,A.,Tang,C.,Fitzsimons, H. L., Mattis, P., and Lawlor, P. A., et al. (2007). Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. Lancet 369, 2097-2105.
49. Kelly, P. H., and Iversen, S. D. (1976). Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulantinduced locomotor activity in rats. Eur. J. Pharmacol. 40, 45-56.
50. Koe, B. K. (1976). Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain. J. Pharmacol. Exp. Ther. 199, 649-661.
51. Kuroki, T., Meltzer, H. Y., and Ichikawa, J. (2003). 5-HT 2A receptor stimulation by DOI, a 5-HT 2A/2C receptor agonist, potentiates amphetamineinduced dopamine release in rat medial prefrontal cortex and nucleus accumbens. Brain Res. 972, 216-221.
52. Landgraf, R., Frank, E., Aldag, J. M., Neumann, I. D., Sharer, C. A., and Ren, X., et al. (2003). Viral vectormediated gene transfer of the vole V1a vasopressin receptor in the rat septum:improved social discrimination and active social behaviour. Eur. J. Neurosci. 18, 403-411.
53. Leysen, J. E. (2004). 5-HT2 receptors. Curr. Drug Target CNS. Neurol. Disord. 3, 11-26.
54. Liu, S., Bubar, M. J., Lanfranco, M. F., Hillman, G. R., and Cunningham, K.A. (2007). Serotonin(2C) receptor localization in GABA neurons of the rat medial prefrontal cortex: implications for understanding the neurobiology of addiction. Neuroscience 146, 1667-1688.
55. Liu, S., and Cunningham, K. A. (2006). Serotonin(2C) receptors (5HT(2C)R) control expression of cocaine-induced conditioned hyperactivity. Drug Alcohol Depend. 81, 275-282.
56. Lo, W. D., Qu, G., Sferra, T. J., Clark, R., Chen, R., and Johnson, P. R. (1999). Adeno-associated virus-mediated gene transfer to the brain: duration and modulation of expression. Hum. Gene Ther. 10, 201-213.
57. McCown, T. J., Xiao, X., Li, J., Breese, G. R., and Samulski, R. J. (1996). Differential and persistent expression patterns of CNS gene transfer by an adeno-associated virus (AAV) vector. Brain Res. 713, 99-107.
58. McCreary, A. C., and Cunningham, K. A. (1999). The effects of the 5HT2C/2B antagonist SB 206553 on cocaine-induced locomotor activity. Neuropsychopharmacology 20, 556-564.
59. McMahon, L. R., and Cunningham, K. A. (2001). Antagonism of 5-hydroxytryptamine(2a) receptors attenuates the behavioral effects of cocaine in rats. J. Pharmacol. Exp. Ther. 297, 357-363.
60. McMahon, L. R., Filip, M., and Cunningham, K. A. (2001). Differential regulation of the mesoaccumbens circuit by serotonin 5hydroxytryptamine (5-HT)2A and 5-HT2C receptors. J. Neurosci. 21, 7781-7787.
61. Miner, L. A., Backstrom, J. R., Sanders-Bush, E., and Sesack, S. R. (2003). Ultrastructural localization of serotonin2A receptors in the middle layers of the rat prelimbic prefrontal cortex. Neuroscience 116, 107-117.
62. Miner, L. H., Schroeter, S., Blakely, R. D., and Sesack, S. R. (2000). Ultrastructural localization of the serotonin transporter in superficial and deep layers of the rat prelimbic prefrontal cortex and its spatialrelationshiptodopamineterminals. J. Comp. Neurol. 427, 220-234.
63. Muller, C. P., and Huston, J. P. (2006). Determining the regionspecific contributions of 5-HT receptors to the psychostimulant effects of cocaine. Trends Pharmacol. Sci. 27, 105-112.
64. Nic Dhonnchadha, B. A., and Cunningham, K. A. (2008). Serotonergic mechanisms in addiction-related memories. Behav. Brain Res. 195, 39-53.
65. Nic Dhonnchadha, B. A., Fox, R. G., Stutz, S. J., Rice, K. C., and Cunningham, K. A. (2009). Blockade of the serotonin 5-HT2A receptor suppresses cue-evoked reinstatement of cocaine-seeking behavior in a rat self-administration model. Behav. Neurosci. 123, 382-396.
66. Nocjar, C., Roth, B. L., and Pehek, E. A. (2002). Localization of 5-HT(2A) receptors on dopamine cells in subnuclei of the midbrain A10 cell group. Neuroscience 111, 163-176.
67. Olijslagers, J. E., Werkman, T. R., McCreary, A. C., Siarey, R., Kruse, C. G., and Wadman, W. J. (2004). 5-HT2 receptors differentially modulate dopaminemediated auto-inhibition in A9 and A10 midbrain areas of the rat. Neuropharmacology 46, 504-510.
68. O'Neill, M. F., Heron-Maxwell, C. L., and Shaw,G. (1999). 5-HT2 receptor antagonism reduces hyperactivity induced by amphetamine, cocaine, and MK-801 but not D1 agonist CAPB. Pharmacol. Biochem. Behav. 63, 237-243.
69. Paxinos,W., and Watson, C. (1998). The Rat Brain in Stereotaxic Coordinates, 4th Edn. San Diego, CA: Academic Press.
70. Peroutka, S. J. (1986). Pharmacological differentiation and characterization of 5-HT1A, 5-HT1B, and 5-HT1C binding sites in rat frontal cortex. J. Neurochem. 47, 529-540.
71. Pessia, M., Jiang, Z.-G., North, R. A., and Johnson, S. W. (1994). Actions of 5-hydroxytryptamine on ventral tegmental area neurons of the rat in vitro. Brain Res. 654, 324-330.
72. Phillipson, O. T. (1979). The cytoarchitecture of the interfascicular nucleus and ventral tegmental area of Tsai in the rat. J. Comp. Neurol. 187, 85-98.
73. Pliakas, A. M., Carlson, R. R., Neve, R. L., Konradi, C., Nestler, E. J., and Carlezon, W. A. Jr. (2001). Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element-binding protein expression in nucleus accumbens. J. Neurosci. 21, 7397-7403.
74. Pockros, L. A., Pentkowski, N. S., Swinford, S. E., and Neisewander, J. L. (2011). Blockade of 5-HT2A receptors in the medial prefrontal cortex attenuates reinstatement of cueelicited cocaine-seeking behavior in rats. Psychopharmacology (Berl.) 213, 307-320.
75. Pollandt, S.W., Orozco-Cabal, L., Scott, M. T., Liu, J., Krishnan, B., Hillman, G. R., et al. (2005). CRF1/2- Immunoreactivity in the Frontolimbic Circuitry is Increased after Acute and Decreased after Protracted Withdrawal from Repeated Cocaine Administration in Rats. Program No. 682.2, Neuroscience 2005 Abstracts, Washington: Society for Neuroscience, Online.
76. Ross, J. D., Herin, D. V., Frankel, P. S., Thomas,M. L.,and Cunningham,K. A. (2006). Chronic treatment with a serotonin(2) receptor (5-HT(2)R) agonist modulates the behavioral and cellular response to (+)-3,4- methylenedioxymethamphetamine [(+)-MDMA]. Drug Alcohol Depend. 81, 117-127.
77. Roth, B. L., Palvimaki, E.-P., Berry, S., Khan, N., Sachs, N., and Uluer, A., et al. (1995). 5-Hydroxytryptamine2A (5-HT2A) receptor desensitization can occur without down-regulation. J. Pharmacol. Exp. Ther. 275, 1638-1646.
78. Rothman, R. B., Baumann, M. H., Savage, J. E., Rauser, L., McBride, A., and Hufeisen, S. J., et al. (2000). Evidence for possible involvement of 5-HT2B receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications. Circulation 102, 2836-2841.
79. Schmidt, C. J., Fadayel, G. M., Sullivan, C. K.,and Taylor,V. L. (1992). 5-HT2 Receptors exert a state-dependent regulation of dopaminergic function: Studies with MDL 100,907 and the amphetamine analogue, 3,4-methylenedioxymethamphetamine. Eur. J. Pharmacol. 223, 65-74.
80. Shank, E. J., Seitz, P. K., Bubar, M. J., Stutz, S. J., and Cunningham, K. A. (2007). Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity. Behav. Neurosci. 121, 1224-1233.
81. St Martin, J. L., Klucken, J., Outeiro, T. F., Nguyen, P., Keller-McGandy, C., and Cantuti-Castelvetri, I., et al. (2007). Dopaminergic neuron loss and up-regulation of chaperone protein mRNA induced by targeted over-expression of alpha-synuclein in mouse substantia nigra. J. Neurochem. 100, 1449-1457.
82. Stone, I. M., Lurie, D. I., Kelley, M. W., and Poulsen, D. J. (2005). Adeno-associated virusmediated gene transfer to hair cells and support cells of the murine cochlea. Mol. Ther. 11, 843-848.
83. Swanson, L. W. (1982). The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res. Bull. 9, 321-353.
84. Szucs, R. P., Frankel, P. S., McMahon, L. R., and Cunningham, K. A. (2005). Relationship of cocaineinduced c-Fos expression to behaviors and the role of serotonin 5-HT2A receptors in cocaine-induced c-Fos expression. Behav. Neurosci. 119, 1173-1183.
85. Walsh, S. L., and Cunningham, K. A. (1997). Serotonergic mechanisms involved in the discriminative stimulus, reinforcing and subjective effects of cocaine. Psychopharmacology (Berl.) 130, 41-58.
86. White, L. A., Eaton, M. J., Castro, M. C., Klose, K. J., Globus, M. Y. T., Shaw, G., et al. (1994). Distinct regulatory pathways control neurofilament expression and neurotransmitter synthesis in immortalized serotonergic neurons. J. Neurosci. 14, 6744-6753.
87. Wu, P., Ye, Y., and Svendsen, C. N. (2002). Transduction of human neural progenitor cells using recombinant adeno-associated viral vectors. Gene Ther. 9, 245-255.
88. Xiao,X.,Li,J.,and Samulski,R. J. (1998). Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus. J. Virol. 72, 2224-2232.
89. Xu, T., and Pandey, S. C. (2000). Cellular localization of serotonin(2A) (5HT(2A))receptorsintheratbrain. Brain Res. Bull. 51, 499-505.
90. Yamaguchi, T., Sheen, W., and Morales, M. (2007). Glutamatergic neurons are present in the rat ventral tegmental area. Eur. J. Neurosci. 25,106-118.
91. Zayara, A. E., McIver, G., Valdivia, P. N., Lominac, K. D., McCreary, A. C., and Szumlinski, K. K. (2011). Blockade of nucleus accumbens 5HT2A and 5-HT2C receptors prevents the expression of cocaineinduced behavioral and neurochemical sensitization in rats. Psychopharmacology (Berl.) 213, 321-335.