Schedule dependence of the interaction of naloxone and chlordiazepoxide

Reports that the opiate antagonist, naloxone, blocks the anticonflict effects of diazepam and chlordiazepoxide suggest endogenous opioid involvement in the anxiolytic actions of the benzodiazepines. However, naloxone's ability to antagonize the anticonflict effects of the benzodiazepines is not universal, but schedule specific. The present experiments investigated the importance of the timing of conflict periods and control of reinforcement on the naloxone-benzodiazepine interaction. We tested the effects of naloxone (3 mg/kg, IP) and chlordiazepoxide (5 mg/kg, IP) on acquisition of a successive discrimination schedule, with nonreward periods similar in length and frequency to those of signalled DRL, and on an FI60-s schedule. Chlordiazepoxide increased rewarded responding and, unexpectedly, decreased nonrewarded responding during acquisition of successive discrimination. This reduction in nonrewarded responding was reversed by naloxone. Under the FI60 schedule, chlordiazepoxide increased nonrewarded responding, an effect that was totally blocked by naloxone at the beginning of the FI. Naloxone's ability to reverse the response-releasing effect of chlordiazepoxide decreased later in the FI. These results suggest endogenous opioid systems are involved in the anxiolytic actions of the benzodiazepines when the animal is adapting to recently introduced conflict. Once adaptation occurs, other neurotransmitter systems mediate the actions of the benzodiazepines.