Manipulations of Serotonin Function in the Nucleus Accumbens Core Produce Differential Effects on Ethanol and Sucrose Seeking and Intake

OBJECTIVE: Behaviorally relevant stimuli, including alcohol, are processed through the nucleus accumbens/ventral tegmental area (VTA)/prefrontal cortex circuit. It is hypothesized that serotonin affects ethanol-directed behaviors by interacting with this system via projections from the dorsal raphe to the nucleus accumbens and VTA. The current studies utilized two different operant paradigms, one focusing on reinforcer seeking and one focusing on reinforcer self-administration (both with an ethanol and a sucrose solution as the reinforcer) to elucidate serotonin-specific regulation of these behaviors. METHODS: The present experiments assessed the effects of microinjections of a serotonin1B agonist (CGS12066B) and a serotonin1A agonist (8-OH-DPAT) in the nucleus accumbens core on ethanol- and sucrose-reinforced seeking and intake. In four separate experiments, male Long-Evans rats were trained to complete a single response requirement that resulted in access to 10% ethanol or 2% sucrose for a 20-min drinking period. RESULTS: Before microinjections, ethanol-reinforced subjects were consuming an average of 0.5-0.95 g/kg ethanol and making 50-100 responses during intermittent nonreinforced sham (no drug) sessions (sucrose groups had similar baseline response levels). In summary, findings from the four experiments showed the following: (1) manipulations of serotonin function that had effects on ethanol-reinforced responding had either no effect or less pronounced effects on sucrose-reinforced responding; (2) administration of the serotonin1B agonist decreased seeking behaviors to a greater degree than drinking behaviors; and (3) administration of the serotonin1A agonist decreased ethanol intake but not seeking with no impact at all on sucrose-reinforced behaviors. CONCLUSIONS: Manipulations of serotonin activity in the nucleus accumbens core had little effect on sucrose-reinforced behaviors and differential effects on ethanol seeking versus intake, suggesting that this area may play a complex but selective role in the stimulus processing of external and internal alcohol-associated cues.