Abstract
Rationale
It has been suggested that the increase in serotonin transmission induced by indirect agonists such as fenfluramine and fluoxetine attenuates cue-elicited reinstatement of cocaine-seeking in rats through a 5-HT2C receptor-dependent mechanism.
Objective
We investigated whether Ro 60-0175, a nonselective 5-HT2B–2C agonist, influences cue-elicited reinstatement of cocaine-seeking behavior. We evaluated the 5-HT2C receptor’s role in Ro 60-0175 by studying its interaction with SB-242,084, a selective 5-HT2C antagonist. The study also explored whether Ro 60-0175 influences cue-elicited seeking behavior associated with sucrose, a highly palatable nutritive reinforcer.
Materials and methods
Different groups of free-feeding rats were trained to associate discriminative stimuli (SDs) with the availability of cocaine or a sucrose pellet or no-reward in two-lever operant cages. Cocaine and sucrose pellets were available under an FR1 schedule of reinforcement, and each reinforcer was followed by a 20-s timeout signaled by a cue light coming above the active lever. After extinction of reinforced responding in the absence of cue, the reinforcer-associated stimuli were reintroduced in reinstatement sessions in which reinforcers were withheld.
Results
Ro 60-0175, at IP doses from 0.1 to 1 mg/kg, dose-dependently reduced cocaine-seeking behavior, while 1 mg/kg had no such effect for the sucrose pellet. Pretreatment with 1 mg/kg SC SB-242,084 completely prevented the effect on cocaine-seeking behavior.
Conclusions
These findings, provided they can be extrapolated to abstinent human addicts, suggest therapeutic potential for the selective 5-HT2C agonist in preventing cue-controlled cocaine-seeking and relapse.
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Acknowledgment
We are grateful to Dr. Ennio Esposito for valuable comments on an earlier version of the manuscript. A preliminary report on this research was presented at the 2005 Annual Meeting of the Society for Neuroscience.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-008-1146-3
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Burbassi, S., Cervo, L. Stimulation of serotonin2C receptors influences cocaine-seeking behavior in response to drug-associated stimuli in rats. Psychopharmacology 196, 15–27 (2008). https://doi.org/10.1007/s00213-007-0916-7
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DOI: https://doi.org/10.1007/s00213-007-0916-7