Journal Article

Stimulation of serotonin sub(2C) receptors influences cocaine-seeking behavior in response to drug-associated stimuli in rats

Burbassi, Silvia, Cervo, Luigi

2008

Overview

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-HT sub(2C) receptor-dependent mechanism. Objective: We investigated whether Ro 60-0175, a nonselective 5-HT sub(2B-2C) agonist, influences cue-elicited reinstatement of cocaine-seeking behavior. We evaluated the 5-HT sub(2C) receptor's role in Ro 60-0175 by studying its interaction with SB-242,084, a selective 5-HT sub(2C) 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 (S super(D)s) 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-HT sub(2C) agonist in preventing cue-controlled cocaine-seeking and relapse.