Preference for a cocaine-associated environment is attenuated by augmentedaccumbal serotonin in cocaine withdrawn rats

Rationale : Recent studies have found decreased serotonin (5-HT) transmissi on within the nucleus accumbens following withdrawal from chronic cocaine. Objective: We sought to investigate whether increasing brain 5-HT levels wo uld decrease behavioral responses that occur following cocaine withdrawal, namely increased preference for a cocaine environment and anxiety. Methods: The conditioned place preference and the defensive burying paradigms were used to measure the behavioral responses that occur 1 week following cocain e withdrawal. Results: We show that pharmacological agents that increase 5- HT transmission (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the prefe rence of subchronically cocaine-treated, abstinent rats for a cocaine-assoc iated environment. Similar results were seen when sertraline was microinjec ted into the nucleus accumbens. Conversely, rats acutely conditioned with c ocaine showed an increased preference for a cocaine-associated environment when pretreated with these drugs. Sertraline also decreased the heightened anxiety-like behaviors found in subchronically treated cocaine rats. Conclu sions: These results indicate that drugs that aug ment 5-HT function may re duce the desire for cocaine following cocaine withdrawal, and thus facilita te cocaine abstinence in dependent subjects.