Ding Zheng-Ming, Ingraham Cynthia M, Rodd Zachary A, McBride William J
Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA
Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
J Psychopharmacol. 2015 Jun;29(6):725-33. doi: 10.1177/0269881115581982. Epub 2015 Apr 28.
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.
乙醇在伏隔核壳部（NACsh）具有强化作用，但其潜在机制仍不清楚。乙醇可增强γ-氨基丁酸A（GABAA）、γ-氨基丁酸B（GABAB）和5-羟色胺3（5-HT3）受体的功能。因此，本研究检验了以下假设：这些受体的激活参与了乙醇在NACsh中的强化作用。采用颅内自我给药（ICSA）程序评估乙醇在嗜酒（P）大鼠NACsh中的强化作用。ICSA包括七个阶段：四个阶段用于建立向NACsh自我输注150mg%乙醇的行为；第5和第6阶段同时输注乙醇加一种浓度的GABAA拮抗剂荷包牡丹碱（10或100μM）、GABAB拮抗剂SCH 50911（50、75或100μM）或5-HT3受体拮抗剂扎考必利（10或100μM）；第7阶段单独输注150mg%乙醇。所有组均向NACsh自我输注乙醇，并且在习得阶段能够轻松区分活动杆和非活动杆。共同输注100μM（而非10μM）的荷包牡丹碱或扎考必利在第5和第6阶段显著降低了活动反应。共同输注75μM（而非50或100μM）的SCH 50911显著减弱了对乙醇的反应。总体而言，结果表明乙醇在NACsh中的强化作用可能受局部GABAA、GABAB和5-HT3受体激活的调节。
