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Four rats were trained on concurrent schedules of shock avoidance and timeout from avoidance, where responses on one lever postponed shock and responses on another lever occasionally (VI 45 sec schedule) produced a 2-min timeout during which the avoidance schedule was suspended. These procedures maintained stable rates of responding on both levers, providing a baseline for studying the effects of drugs on behavior under different types of aversive control (shock avoidance and timeout from avoidance). In the first experiment the effects of ethanol (0.5, 1.0, 1.5, and 2.0 g/kg) and an opiate antagonist, naltrexone (1 mg/kg) were assessed alone and in combination. Ethanol produced a dose-dependent decrease in avoidance characterized by increased shock rates and decreased response rates. At the same time, however, responding on the timeout lever generally increased relative to avoidance lever rates. All of these effects were largely confined to the early parts of the 2-hr session, when blood-ethanol levels were relatively high. Naltrexone had no effect on performances and did not interact with ethanol. In a second experiment, the effects of the benzodiazepine antagonist CGS 8216 were studied alone, and in combination with ethanol. CGS 8216 (5 mg/kg) generally disrupted both avoidance and timeout responding but did not reverse ethanol actions.

The present study assessed the effects of ethanol and naloxone on the extinction of a jump-up avoidance response in Sprague-Dawley rats. Rats were first trained to jump onto a shelf to escape or avoid shock (0.5 mA). Upon reaching an acquisition criterion of 8 consecutive avoidance trials, animals were removed from the apparatus and exposed to 1 of 4 doses of ethanol (0, 1.0, 2.0, or 2.5 g/kg), and either naloxone (3 mg/kg) or saline. Rats were then returned to the conditioning apparatus with the shock turned off, and resistance to extinction was assessed. Ethanol had biphasic effects with low doses (1 g/kg) facilitating, and higher doses (2 and 2.5 g/kg) suppressing number of extinction responses by comparison to controls. Naloxone did not influence the course of extinction, and did not reverse any of the effects of ethanol. These results did not support the hypothesis that the effects of ethanol on aversively-motivated behavior are opioid-mediated.

Several recent studies have suggested that some effects of ethanol may be mediated by the opioid receptor systems. The present study examined the possibility of a common link between ethanol and opiates by determining whether the effects of ethanol on rat's free operant avoidance behavior could be reversed by the opiate antagonist naltrexone. In Experiment 1 ethanol produced a dose-dependent impairment of avoidance performance (characterized by a decrease in response rate and/or an increase in shock rate) in all three subjects. Naltrexone (3 mg/kg) alone suppressed avoidance rates, but failed to reverse or reduce the effects of ethanol. In contrast to the expectations of the "common-link" hypothesis, the greatest impairment of performance was observed after high doses of ethanol in combination with naltrexone. In Experiment 2 the effects of chronic naltrexone administration were examined. Since previous research has suggested that chronic treatment with opiate antagonists produces a heightened sensitivity to opiate agonists and antagonists, Experiment 2 addressed the issue of whether sensitization to naltrexone would transfer to ethanol. Although increased sensitivity to the rate-decreasing effects of naltrexone was observed, there was no evidence of heightened sensitivity to ethanol. Taken together the results provided little support for the hypothesis that the effects of ethanol on avoidance performance are mediated by the opiate receptor system.

Ethanol had biphasic effects on jump-up avoidance extinction with low doses (1 g/kg) increasing, and high doses (2.5 g/kg) decreasing number of trials to extinction criterion. In Experiment 1 these doses of ethanol were studied alone, and in combination with RO 15-4513 (0.3, 3 or 6 mg/kg). The stimulation of responding produced by low ethanol doses was reversed by 3 and 6 mg/kg doses of RO 15-4513 which had intrinsic suppressive effects, but the depressed responding produced by higher ethanol doses was not attenuated by RO 15-4513. Experiment 2 analysed the interaction between ethanol and benzodiazepine antagonists RO 15-1788 and CGS 8216. RO 15-1788 did not have intrinsic action and did not interact with ethanol. CGS 8216 showed an intrinsic suppressive action much like RO 15-4513, and also reversed the stimulation produced by low dose ethanol, but not the effects of the high dose. Experiment 3 showed that the benzodiazepine agonist, chlordiazepoxide, had effects much like low dose ethanol which were reversed by CGS 8216 and RO 15-4513. The major conclusions were that RO 15-4513 and CGS 8216 possess inverse agonist properties which may cancel out the effects of alcohol under certain circumstances.

The present study used the aggressive display of Betta splendens in response to a mirror as an index of the effects of ethanol and the opiate antagonist, naltrexone. Naltrexone produces an opiate receptor blockade and thus provided a test of the hypothesis that ethanol effects on aggression are mediated by the opioid system. Eighty fish were randomly assigned to one of eight groups in a 4 X 2 factorial design with Ethanol (0, 0.25, 0.50, and 0.75 g%) and Naltrexone (0 and 5 mg/l) as the main factors. The 0.75 g% dose of ethanol reliably suppressed aggressive display as measured by number of gill show responses, but lower doses had no effect or tended to increase aggressive display. At the same time, all doses of ethanol increased arousal in the fish as measured by airgulping. Naltrexone alone did not have effects on aggression or arousal, and did not interact with ethanol on either measure. Thus the results did not support the ethanol-opioid common-link hypothesis.