0 zyxwvutsrqponml t45-6008/97/2102-0368$03.00/0 ALCOHOLISM: CLINICAL zyxwvutsrqponmlk AND EXPERIMENTAL RESEARCH zyxwvutsrqpon Vol. zy 21, No. 2 April 1997 Ethanol Inhibits Single-Unit Responses in the Nucleus Accumbens Evoked by Stimulation of the Basolateral Nucleus of the Amygdala Jose R. Criado, Rong-Sheng Lee, Greta I. Berg, and Steven J. Henriksen We studied the actions of intoxicating doses of ethanol on excitatory inputsfrom the basolateralnucleus of the amygdala, a major afferent system projecting to the nucleus accumbens (NAcc). In view of the hypothesized role of opioid receptors on the effects of ethanol on NAcc physiology, we also explored whether naloxone modulates ethanol-induced suppression of NAcc excitability in halothaneanes- thetized and freely moving unanesthetized rats. lntraperitoneal ad- ministration of ethanol (1.2-1.4 g/kg) markedly suppressed a sub- group of amygdala-activated NAcc neurons. The ethanol-induced reduction in amygdala-activated NAcc neuronswas not reversed by naloxone (5.0 mg/kg, intraperitoneally). Moreover, naloxone had no effect on the supressive effects of ethanol on NAcc spontaneous activity in either halothane-anesthetized or unanesthetired freely moving preparations. These findings suggest that opiate mecha- nismseither are not participatingor are not solely responsiblefor the inhibitory effects of acute intoxicating doses of ethanol on NAcc physiology. Key Words: Alcohol, Nucleus Accumbens, Amygdala, Single Unit Recordings, Naloxone. CONSISTENT effect of ethanol on neuronal pharma- A cology is the suppression of glutamatergic-related ex- citatory synaptic transmission,”2 which has been hypothe- sized to play an important role in the intoxicating behavioral effects of ethan01.~-~ Several lines of evidence suggest a role for the nucleus accumbens (NAcc) and the mesocorticolimbic system in the reinforcing properties of ethanol and its abuse ~ o t e n t i a l . ~ - ~ Because the activity of NAcc neurons strongly depends on excitatory inputs from cortical and subcortical limbic afferents,lo-l4 our studies have focused on characterizing the effects of ethanol on these inputs. Our initial findings indicated that, although systemic administration of ethanol had no effect on the excitability of fimbria-activated neurons in the NAcc-core, it suppressed glutamate-activated and spontaneously active NAcc ne~rons.’~ These data suggest that only some of the zyxwvu From the Alcohol Research Center and the Department of Neuropharma- Received for publication December 19, 1995; accepted December 6, 1996 This research was supported by a National Institute on Alcoholism and Alcohol Abuse center grant zyxwvutsrq P50-AAO6420, and Alcohol Research Center Training grant T32-AAO7456, and National Institute of Drug Abuse grant Reprint requests: Steven J. Henriksen, Ph.D., Department of Neurophar- macology, The Scripps Research Institute, Blake Building CVN-13, 10550 North Torrey Pines Road, La Jolla, CA 92037. cology, The Scripps Research Institute, La Jolla, California. DA-08301 (S.J.H.). Copyright zyxwvutsrqpon 0 I997 by The Research Society on Alcoholism. 368 excitatory mechanisms regulating NAcc function are sensi- tive to intoxicating doses of ethanol. Anatomical and electrophysiological evidence suggests that the basolateral nucleus of the amygdala projects exci- tatory afferents to NAcc neurons.16-21 Whereas these amygdaloid excitatory inputs innervate both the core and the shell regions of the NAcc,~’.~~ very little is known about their interactions with ethanol. The initial results from both in vivo and in vitro electrophysiological studies suggest that ethanol suppresses NAcc physiology through its actions on excitatory processes on a subpopulation of NAcc neu- ron~.~~*~~*~~ In recent studies, naloxone, an opioid receptor antagonist, was found to antagonize the inhibitory effects of ethanol on NAcc glutamatergic synaptic transmission, in ~itro.’~ These findings are in concordance with previous studies supporting a role for opioid receptors in ethanol self-administrati~n~~~~’ and, interestingly, in human alco- holi~m.~~*~~ In contrast, a recent study demonstrated that naloxone had no effect on ethanol-induced suppression of evoked N-methybaspartate (NMDA) currents in NAcc neurons in vitro, suggesting that not all of the suppressive effects of ethanol on NAcc neurons may involve opioid systems.25To understand further the effects of acute eth- anol on NAcc physiology, we have studied the actions of ethanol on amygdala-evoked inputs projecting to the NAcc. Furthermore, as an initial approach to understand the role of opiates in ethanol reinforcement, we explored the pos- sibility that ethanol-induced suppression of NAcc excitabil- ity in vivo is reversed by the opioid receptor antagonist naloxone. MATERIALS AND METHODS Subjects Male Sprague-Dawley rats (Charles River Laboratory, Hollister, CA), weighing 260-325 g at the time of surgery, were used in this study. Rats were allowed a 1-week acclimation period before any experimental pro- tocol. The animals used in freely moving electrophysiologicalexperiments were housed individually, with ad libitum access to food and water and maintained on a reversed 12-hr light cycle (on at 22:OO hr, off at 1O:OO hr). Animal maintenance and experimental procedures were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. zyxwv Alcohol Clin Exp Res, Vol21, No 2, 1997: pp 368-374