The reinforcing effects of ethanol within the nucleus accumbens shell involve activation of local GABA and serotonin receptors

Ethanol is reinforcing within the nucleus accumbens shell (NACsh), but the underlying mechanisms remain unclear. Ethanol can potentiate the function of the GABA(A), GABA(B), and serotonin-3 (5-HT3) receptors. Therefore, the current study tested the hypothesis that activation of these receptors would be involved in the reinforcing effects of ethanol in the NACsh. An intracranial self-administration (ICSA) procedure was used to assess the reinforcing effects of ethanol in the NACsh of alcohol preferring (P) rats. The ICSA consisted of seven sessions: four sessions to establish 150 mg% ethanol self-infusion into the NACsh; sessions 5 and 6 with co-infusion of ethanol plus one concentration of the GABA(A) antagonist bicuculline (10 or 100 mu M), the GABA(B) antagonist SCH 50911 (50, 75 or 100 mu M), or the 5-HT3 receptor antagonist zacopride (10 or 100 mu M); and session 7 with 150 mg% ethanol alone. All groups self-infused ethanol into the NACsh and readily discriminated the active from inactive lever during the acquisition sessions. Co-infusion of 100 mu M, but not 10 mu M, bicuculline or zacopride significantly decreased active responses during sessions 5 and 6. Co-infusion of 75 mu M, but not 50 or 100 mu M, SCH 50911 significantly attenuated responses for ethanol. Overall, the results suggest that the reinforcing effects of ethanol in the NACsh may be modulated by activation of local GABA(A), GABA(B) and 5-HT3 receptors.