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The role of serotonin-1B receptors (5-HT_1BRs) in modulating cocaine abuse-related behaviors has been controversial due to discrepancies between pharmacological and gene knockout approaches and opposite influences on cocaine self-administration versus cocaine-seeking behavior. We hypothesized that modulation of these behaviors via 5-HT_1BRs in the mesolimbic pathway may vary depending on the stage of the addiction cycle.

To test this hypothesis, we examined the effects of increasing 5-HT_1BR production by microinfusing a viral vector expressing either green fluorescent protein and 5-HT_1BR or green fluorescent protein alone into the medial nucleus accumbens shell of rats either during maintenance of cocaine self-administration (i.e., active drug use) or during protracted withdrawal.

5-HT_1BR receptor gene transfer during maintenance shifted the dose …