Functional status of the serotonin 5-HT 2C receptor (5-HT 2C R) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence

Neuropsychopharmacology

Volumn 39, Issue 2, 2014, Pages 360-372

  Anastasio, Noelle C ^a   Stutz, Sonja J ^a   Fox, Robert G ^a   Sears, Robert M ^b   Emeson, Ronald B ^c   Dileone, Ralph J ^b   O'Neil, Richard T ^c   Fink, Latham H ^a   Li, Dingge ^a   Green, Thomas A ^a   Gerard Moeller, F ^d   Cunningham, Kathryn A ^a  

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

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

5 HT2C receptor; cocaine; cue reactivity; impulsive action; prefrontal cortex; RNA editing

Indexed keywords

MESSENGER RNA; MESSENGER RNA PRECURSOR; SEROTONIN 2C RECEPTOR;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; COCAINE DEPENDENCE; CONTROLLED STUDY; FUNCTIONAL STATUS; GENE LOSS; GENETIC VARIABILITY; IMMUNOREACTIVITY; IMPULSIVENESS; INTERNALIZATION; MALE; NONHUMAN; PHENOTYPE; PREFRONTAL CORTEX; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; REACTION TIME; RELAPSE; RELIABILITY; REPRODUCIBILITY; SIGNAL TRANSDUCTION; TIGHT JUNCTION; ANIMAL; ANIMAL BEHAVIOR; DRUG SELF ADMINISTRATION; GENETICS; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; RECURRENT DISEASE; SPRAGUE DAWLEY RAT;

ANIMALS; BEHAVIOR, ANIMAL; COCAINE-RELATED DISORDERS; MALE; PHENOTYPE; PREFRONTAL CORTEX; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR, SEROTONIN, 5-HT2C; RECURRENCE; SELF ADMINISTRATION;

EID: 84890551235     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2013.199     Document Type: Article

References (65)

1. Abbas AI, Yadav PN, Yao WD, Arbuckle MI, Grant SG, Caron MG et al (2009). PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptors. J Neurosci 29: 7124-7136.
2. Anastasio NC, Gilbertson SR, Bubar MJ, Agarkov A, Stutz SJ Jeng YJ et al (2013a). Peptide inhibitors disrupt the serotonin 5-HT2C receptor interaction with phosphatase and tensin homolog to allosterically modulate cellular signaling and behavior. J Neurosci 33: 1615-1630.
3. Anastasio NC, Lanfranco MF, Bubar MJ, Seitz PK, Stutz SJ McGinnis AG et al (2010). Serotonin 5-HT(2C) receptor protein expression is enriched in synaptosomal and post-synaptic compartments of rat cortex. J Neurochem 113: 1504-1515.
4. Anastasio NC, Stoffel EC, Fox RG, Bubar MJ, Rice KC, Moeller FG et al (2011). Serotonin (5-hydroxytryptamine) 5-HT2A receptor: Association with inherent and cocaine-evoked behavioral disinhibition in rats. Behav Pharmacol 22: 248-261.
5. Becamel C, Alonso G, Galeotti N, Demey E, Jouin P, Ullmer C et al (2002). Synaptic multiprotein complexes associated with 5-HT(2C) receptors: a proteomic approach. EMBO J 21: 2332-2342.
6. Belin D, Mar AC, Dalley JW, Robbins TW, Everitt BJ (2008). High impulsivity predicts the switch to compulsive cocaine-taking. Science 320: 1352-1355.
7. Bentley DR, Balasubramanian S, Swerdlow HP, Smith GP, Milton J Brown CG et al (2008). Accurate whole human genome sequencing using reversible terminator chemistry. Nature 456: 53-59.
8. Besson M, Pelloux Y, Dilleen R, Theobald DE, Lyon A, Belin Rauscent A et al (2013). Cocaine modulation of frontostriatal expression of Zif268, D2, and 5-HT2c receptors in high and low impulsive rats. Neuropsychopharmacology 38: 1963-1973.
9. Bradberry CW, Rubino SR (2004). Phasic alterations in dopamine and serotonin release in striatum and prefrontal cortex in response to cocaine predictive cues in behaving rhesus macaques. Neuropsychopharmacology 29: 676-685.
10. Breukel AI, Besselsen E, Ghijsen WE (1997). Synaptosomes. A model system to study release of multiple classes of neurotransmitters. Methods Mol Biol 72: 33-47.
11. Bubar MJ, Stutz SJ, Cunningham KA (2011). 5-HT(2C) receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway. PLoS ONE 6: e20508.
12. Burns CM, Chu H, Rueter SM, Hutchinson LK, Canton H, Sanders Bush E et al (1997). Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature 387: 303-308.
13. Carpenter KM, Schreiber E, Church S, McDowell D (2006). Drug Stroop performance: relationships with primary substance of use and treatment outcome in a drug-dependent outpatient sample. Addict Behav 31: 174-181.
14. Carter BL, Tiffany ST (1999). Cue-reactivity and the future of addiction research. Addiction 94: 349-351.
15. Chen BT, Yau HJ, Hatch C, Kusumoto-Yoshida I, Cho SL Hopf FW et al (2013). Rescuing cocaine-induced prefrontal cortex hypoactivity prevents compulsive cocaine seeking. Nature 496: 359-362.
16. Cunningham KA, Anastasio NC (2013). Serotonin at the nexus of impulsivity and cue ceactivity in cocaine addiction. Neuropharmacology (In press).
17. Cunningham KA, Anastasio NC, Fox RG, Stutz SJ, Bubar MJ Swinford SE et al (2012). Synergism between a serotonin 5-HT2A receptor (5-HT2AR) antagonist and 5-HT2CR agonist suggests new pharmacotherapeutics for cocaine addiction. ACS Chemical Neuroscience 4: 110-121.
18. Cunningham KA, Fox RG, Anastasio NC, Bubar MJ, Stutz SJ Moeller FG et al (2011). Selective serotonin 5-HT2C 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.
19. Dalley JW, Everitt BJ, Robbins TW (2011). Impulsivity, compulsivity and top-down cognitive control. Neuron 69: 680-694.
20. Dalley JW, Fryer TD, Brichard L, Robinson ES, Theobald DE Laane K et al (2007). Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement. Science 315: 1267-1270.
21. Dalley JW, Theobald DE, Eagle DM, Passetti F, Robbins TW (2002). Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex. Neuropsychopharmacology 26: 716-728.
22. Daly TM (2004). Overview of adeno-associated viral vectors. Methods Mol Biol 246: 157-165.
23. Economidou D, Pelloux Y, Robbins TW, Dalley JW, Everitt BJ (2009). High impulsivity predicts relapse to cocaine-seeking after punishment induced abstinence. Biol Psychiatry 65: 851-856.
24. Field M, Cox WM (2008). Attentional bias in addictive behaviors: a review of its development, causes, and consequences. Drug Alcohol Depend 97: 1-20.
25. Fletcher PJ, Rizos Z, Noble K, Higgins GA (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.
26. Fletcher PJ, Rizos Z, Sinyard J, Tampakeras M, Higgins GA (2008). The 5-HT(2C) receptor agonist RO 60-0175 reduces cocaine self-administration and reinstatement induced by the stressor yohimbine and contextual cues. Neuropsychopharmacology 33: 1402-1412.
27. Frijda NH (2010). Impulsive action and motivation. Biol Psychol 84: 570-579.
28. Gavarini S, Becamel C, Altier C, Lory P, Poncet J, Wijnholds J et al (2006). Opposite effects of PSD-95 and MPP3 PDZ proteins on serotonin 5-hydroxytryptamine2C receptor desensitization and membrane stability. Mol Biol Cell 17: 4619-4631.
29. Green CE, Moeller FG, Schmitz JM, Lucke JF, Lane SD, Swann AC et al (2009). Evaluation of heterogeneity in pharmacotherapy trials for drug dependence: a Bayesian approach. Am J Drug Alcohol Abuse 35: 95-102.
30. Grottick AJ, Corrigall WA, Higgins GA (2001). Activation of 5-HT2C receptors reduces the locomotor and rewarding effects of nicotine. Psychopharmacology 157: 292-298.
31. Herrick-Davis K, Grinde E, Niswender CM (1999). Serotonin 5-HT2C receptor RNA editing alters receptor basal activity: implications for serotonergic signal transduction. J Neurochem 73: 1711-1717.
32. Hommel JD, Sears RM, Georgescu D, Simmons DL, DiLeone RJ (2003). Local gene knockdown in the brain using viral-mediated RNA interference. Nat Med 9: 1539-1544.
33. Hoyer D, Hannon JP, Martin GR (2002). Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71: 533-554.
34. Kalivas PW, Volkow ND (2005). The neural basis of addiction: A pathology of motivation and choice. Am J Psychiatry 162: 1403-1413.
35. Keppel G (1973). Design and Analysis: A Researcher's Handbook. Prentice-Hall, Inc.: Englewood Cliffs, NJ, USA.
36. Komlosi G, Molnar G, Rozsa M, Olah S, Barzo P, Tamas G (2012). Fluoxetine (prozac) and serotonin act on excitatory synaptic transmission to suppress single layer 2/3 pyramidal neurontriggered cell assemblies in the human prefrontal cortex. J Neurosci 32: 16369-16378.
37. Koob GF, Volkow ND (2010). Neurocircuitry of addiction. Neuropsychopharmacology 35: 217-238.
38. Koya E, Uejima JL, Wihbey KA, Bossert JM, Hope BT, Shaham Y (2009). Role of ventral medial prefrontal cortex in incubation of cocaine craving. Neuropharmacology 56(Suppl 1): 177-185.
39. LaLumiere RT, Smith KC, Kalivas PW (2012). Neural circuit competition in cocaine-seeking: roles of the infralimbic cortex and nucleus accumbens shell. Eur J Neurosci 35: 614-622.
40. Lanfranco MF, Seitz PK, Morabito MV, Emeson RB, Sanders-Bush E Cunningham KA (2009). An innovative real-time PCR method to measure changes in RNA editing of the serotonin 2C receptor (5-HT(2C)R) in brain. J Neurosci Methods 179: 247-257.
41. Leff SE, Spratt SK, Snyder RO, Mandel RJ (1999). Long-term restoration of striatal L-aromatic amino acid decarboxylase activity using recombinant adeno-associated viral vector gene transfer in a rodent model of Parkinson's disease. Neuroscience 92: 185-196.
42. Li X, Wolf ME (2011). Visualization of virus-infected brain regions using a GFP-illuminating flashlight enables accurate and rapid dissection for biochemical analysis. J Neurosci Methods 201: 177-179.
43. Linley SB, Hoover WB, Vertes RP (2013). Pattern of distribution of serotonergic fibers to the orbitomedial and insular cortex in the rat. J Chem Neuroanat 48-49: 29-45.
44. Liu S, Bubar MJ, Lanfranco MF, Hillman GR, Cunningham KA (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.
45. Liu S, Lane SD, Schmitz JM, Waters AJ, Cunningham KA, Moeller FG (2011). Relationship between attentional bias to cocainerelated stimuli and impulsivity in cocaine-dependent subjects. Am J Drug Alcohol Abuse 37: 117-122.
46. Marion S, Weiner DM, Caron MG (2004). RNA editing induces variation in desensitization and trafficking of 5-hydroxytryptamine 2c receptor isoforms. J Biol Chem 279: 2945-2954.
47. Martin CB, Ramond F, Farrington DT, Aguiar AS Jr., Chevarin C Berthiau AS et al (2013). RNA splicing and editing modulation of 5-HT(2C) receptor function: relevance to anxiety and aggression in VGV mice. Mol Psychiatry 18: 656-665.
48. Millan MJ, Marin P, Bockaert J, la Cour CM (2008). Signaling at G-protein-coupled serotonin receptors: recent advances and future research directions. Trends Pharmacol Sci 29: 454-464.
49. Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC (2001a). Psychiatric aspects of impulsivity. Am J Psychiatry 158: 1783-1793.
50. Moeller FG, Dougherty DM, Barratt ES, Schmitz JM, Swann AC Grabowski J (2001b). The impact of impulsivity on cocaine use and retention in treatment. J Subst Abuse Treat 21: 193-198.
51. Moeller FG, Schmitz JM, Steinberg JL, Green CM, Reist C, Lai LY et al (2007). Citalopram combined with behavioral therapy reduces cocaine use: a double-blind, placebo-controlled trial. Am J Drug Alcohol Abuse 33: 367-378.
52. Morabito MV, Ulbricht RJ, O'Neil RT, Airey DC, Lu P, Zhang B et al (2010). High-throughput multiplexed transcript analysis yields enhanced resolution of 5-hydroxytryptamine 2C receptor mRNA editing profiles. Mol Pharmacol 77: 895-902.
53. Murphy ER, Fernando AB, Urcelay GP, Robinson ES, Mar AC Theobald DE et al (2012). Impulsive behaviour induced by both NMDA receptor antagonism and GABAA receptor activation in rat ventromedial prefrontal cortex. Psychopharmacology 219: 401-410.
54. Parsons LH, Koob GF, Weiss F (1995). Extracellular serotonin is decreased in the nucleus accumbens during withdrawal from cocaine self-administration. Behav Brain Res 73: 225-228.
55. Paxinos G, Watson C (1998). The Rat Brain in Stereotaxic Coordinates. Academic Press: Sydney, Australia.
56. Pentkowski NS, Duke FD, Weber SM, Pockros LA, Teer AP Hamilton EC et al (2010). Stimulation of medial prefrontal cortex serotonin 2C 5-HT2C receptors attenuates cocaine-seeking behavior. Neuropsychopharmacology 35: 2037-2048.
57. Robbins TW (2002). The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology 163: 362-380.
58. Robinson ES, Dalley JW, Theobald DE, Glennon JC, Pezze MA Murphy ER et al (2008). Opposing roles for 5-HT2A and 5-HT2C receptors in the nucleus accumbens on inhibitory response control in the 5-choice serial reaction time task. Neuropsychopharmacology 33: 2398-2406.
59. Volkow ND, Fowler JS, Wang GJ, Baler R, Telang F (2009). Imaging dopamine's role in drug abuse and addiction. Neuropharmacology 56(Suppl 1): 3-8.
60. Voon V, Irvine MA, Derbyshire K, Worbe Y, Lange I, Abbott S et al (2013). Measuring "waiting" impulsivity in substance addictions and binge eating disorder in a novel analogue of rodent serial reaction time task. Biol Psychiatry S0006-3223: 00456-3.
61. Warden MR, Selimbeyoglu A, Mirzabekov JJ, Lo M, Thompson KR Kim SY et al (2012). A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature 492: 428-432.
62. Werry TD, Stewart GD, Crouch MF, Watts A, Sexton PM Christopoulos A (2008). Pharmacology of 5HT(2C) receptormediated ERK1/2 phosphorylation: agonist-specific activation pathways and the impact of RNA editing. Biochem Pharmacol 76: 1276-1287.
63. Winstanley CA, Dalley JW, Theobald DE, Robbins TW (2004a). Fractionating impulsivity: contrasting effects of central 5-HT depletion on different measures of impulsive behavior. Neuropsychopharmacology 29: 1331-1343.
64. Winstanley CA, Theobald DE, Dalley JW, Glennon JC, Robbins TW (2004b). 5-HT2A and 5-HT2C receptor antagonists have opposing effects on a measure of impulsivity: interactions with global 5-HT depletion. Psychopharmacology 176: 376-385.
65. Zhu H, Urban DJ, Blashka J, McPheeters MT, Kroeze WK Mieczkowski P et al (2012). Quantitative analysis of focused a-to-I RNA editing sites by ultra-high-throughput sequencing in psychiatric disorders. PLoS ONE 7: e43227.