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

卷:61

Article

Cunningham, Kathryn A.¹  Fox, Robert G.¹  Anastasio, Noelle C.¹  Bubar, Marcy J.¹  Stutz, Sonja J.¹  Moeller, F. Gerard²  Gilbertson, Scott R.³  Rosenzweig-Lipson, Sharon⁴ 

[1] Univ Texas Med Branch, Addict Res Ctr, Dept Pharmacol & Toxicol, Galveston, TX 77550 USA

[2] Univ Texas Hlth Sci Ctr, Dept Psychiat & Behav Sci, Houston, TX USA

[3] Univ Houston, Dept Chem, Houston, TX USA

[4] Pfizer Global Res & Dev, Neurosci, Groton, CT USA

关键词: 5-HT2C receptor;    Addiction;    Cocaine;    Reward;    Self-administration;    Serotonin;    Sucrose;    WAY 163909;   

DOI  :  10.1016/j.neuropharm.2011.04.034

来源: Elsevier

【 摘 要 】

Serotonin (5-HT) controls affective and motivational aspects of palatable food and drug reward and the 5-HT2C receptor (5-HT2CR) has emerged as a key regulator in this regard. We have evaluated the efficacy of a selective 5-HT2CR agonist, WAY 163909, in cocaine and sucrose self-administration and reinstatement assays employing parallel experimental designs in free-fed rats. WAY 163909 dose-dependently reduced the reinforcing efficacy of cocaine (ID50 = 1.19 mg/kg) and sucrose (ID50 = 0.7 mg/kg) as well as reinstatement (ID50 = 0.5 mg/kg) elicited by exposure to cocaine-associated contextual cues, but not sucrose-associated contextual cues. The ID50 of WAY 163909 predicted to decrease the reinforcing efficacy of cocaine or sucrose as well as reinstatement upon exposure to cocaine-associated cues was similar to 5-12-fold lower than that predicted to suppress horizontal ambulation (ID50 = 5.89 mg/kg) and similar to 2-5-fold lower than that predicted to suppress vertical activity (ID50 = 2.3 mg/kg). Thus, selective stimulation of the 5-HT2CR decreases the reinforcing efficacy of cocaine and sucrose in freely-fed rats, but differentially alters the incentive-salience value of cocaine- vs. sucrose-associated cues at doses that do not impair locomotor activity. Future research is needed to tease apart the precise contribution of 5-HT2CR neurocircuitry in reward and motivation and the learning and memory processes that carry the encoding for associations between environmental cues and consumption of rewarding stimuli. A more complete preclinical evaluation of these questions will ultimately allow educated proof-of-concept trials to test the efficacy of selective 5-HT2CR agonists as adjunctive therapy in chronic health maladies including obesity, eating disorders and drug addiction. This article is part of a Special Issue entitled 'Serotonin: The New Wave'. (C) 2011 Published by Elsevier Ltd.

【 授权许可】

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