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

Abstract

Ethanol is reinforcing within the nucleus accumbens shell (NACsh), but the underlying mechanisms remain unclear. Ethanol can potentiate the function of the GABAA, GABAB, 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 GABAA antagonist bicuculline (10 or 100 µM), the GABAB antagonist SCH 50911 (50, 75 or 100 µM), or the 5-HT3 receptor antagonist zacopride (10 or 100 µM); 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 µM, but not 10 µM, bicuculline or zacopride significantly decreased active responses during sessions 5 and 6. Co-infusion of 75 µM, but not 50 or 100 µM, 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 GABAA, GABAB and 5-HT3 receptors.

Keywords: GABAA receptor; GABAB receptor; Intracranial self-administration; ethanol; nucleus accumbens; serotonin receptor.

Figure 1

Representative placements of microinjection sites in the nucleus accumbens shell for the self-infusion of ethanol. For clarity purpose, the overlapping sites are not included. Circles represent sites within the nucleus accumbens shell and squares represent sites ventral to the nucleus accumbens shell.

Figure 2

Effects of co-infusion of aCSF, 10 or 100 µM bicuculline (a GABA_A receptor antagonist) with 150 mg% ethanol on lever responses for the intracranial self-infusion of ethanol into the nucleus accumbens shell (n = 6–7 / group). * p < 0.05, significantly higher responses than those on the inactive lever. # p < 0.05, significantly lower responses than the average responses on the active lever during acquisition sessions 3 and 4.

Figure 3

Effects of co-infusion of 50, 75 or 100 µM SCH 50911 (a GABA_B receptor antagonist) with 150 mg% ethanol on lever responses for the intracranial self-infusion of ethanol into the nucleus accumbens shell (n = 6 / group). * p < 0.05, significantly higher responses than those on the inactive lever. # p < 0.05, significantly lower responses than the average responses on the active lever during acquisition sessions 3 and 4.

Figure 4

Effects of co-infusion of 10 or 100 µM zacopride (a 5-HT3 receptor antagonist) with 150 mg% ethanol on lever responses for the intracranial self-infusion of ethanol into the nucleus accumbens shell (n = 6–7 / group). * p < 0.05, significantly higher responses than those on the inactive lever. # p < 0.05, significantly lower responses than the average responses on the active lever during acquisition sessions 3 and 4.