Nie Z, Yuan X, Madamba S G, Siggins G R
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
J Pharmacol Exp Ther. 1993 Sep;266(3):1705-12.
The nucleus accumbens septi (NAcc) is a key brain region in the rewarding effects of addictive drugs such as opiates and ethanol. We recently showed that opiate peptides reduced both excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) in NAcc neurons of a slice preparation, with naloxone (Nal) reversal (Yuan et al., 1992). To test other addictive drugs, we used intracellular recording in this rat NAcc slice preparation to investigate ethanol actions on NAcc neuronal properties. Ethanol 22 to 66 mM had little reproducible effect on membrane potential or input slope resistance, but reduced the amplitude of EPSPs evoked by stimulation of the peri-tubercle region ventral to NAcc. Ethanol 22, 44 and 66 mM all significantly decreased the EPSPs evoked by half-maximal stimulation to 80, 60 and 68% of control, respectively. Superfusion of 11 mM ethanol had no effect. To confirm a direct ethanol action on EPSPs, we tested 44 mM ethanol in the presence of 30 microM bicuculline to block IPSPs. In these cells ethanol still decreased EPSP size, suggesting GABAAergic IPSPs are not involved in this effect. The glutamate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione abolished the EPSPs evoked at resting membrane potentials. As ethanol actions mimic those of opiates in reducing EPSPs without effect on resting membrane potentials in the NAcc, we applied the opiate antagonist Nal together with ethanol. Nal 1 to 2 microM significantly reversed ethanol (44 mM) reduction of EPSP amplitude. Thus, our data suggest that a major effect of intoxicating concentrations of ethanol in NAcc is to reduce glutamatergic synaptic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
伏隔核是诸如阿片类药物和乙醇等成瘾性药物产生奖赏效应的关键脑区。我们最近发现，阿片肽可降低脑片制备中伏隔核神经元的兴奋性和抑制性突触后电位（EPSP和IPSP），且可被纳洛酮逆转（Yuan等人，1992年）。为了测试其他成瘾性药物，我们在这种大鼠伏隔核脑片制备中采用细胞内记录来研究乙醇对伏隔核神经元特性的作用。22至66 mM的乙醇对膜电位或输入斜率电阻几乎没有可重复的影响，但可降低对伏隔核腹侧结节周围区域刺激所诱发的EPSP幅度。22、44和66 mM的乙醇分别将半最大刺激所诱发的EPSP显著降低至对照的80%、60%和68%。11 mM乙醇的灌流没有影响。为了证实乙醇对EPSP有直接作用，我们在存在30 microM荷包牡丹碱以阻断IPSP的情况下测试了44 mM乙醇。在这些细胞中，乙醇仍可降低EPSP大小，表明GABAA能IPSP不参与此效应。谷氨酸受体阻断剂6-氰基-7-硝基喹喔啉-2,3-二酮消除了静息膜电位时诱发的EPSP。由于乙醇的作用在降低EPSP方面模仿了阿片类药物，而对伏隔核的静息膜电位没有影响，我们将阿片拮抗剂纳洛酮与乙醇一起应用。1至2 microM的纳洛酮可显著逆转乙醇（44 mM）对EPSP幅度的降低。因此，我们的数据表明，伏隔核中中毒浓度乙醇的主要作用是降低谷氨酸能突触传递。（摘要截选至250词）
