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Stimulation of serotonin2C receptors influences cocaine-seeking behavior in response to drug-associated stimuli in rats

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An Erratum to this article was published on 17 May 2008

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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Correspondence to Luigi Cervo.

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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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