Rationale: Both novelty and naloxone have been reported to modify the anxiolytic-like effect of benzodiazepines in the elevated plus maze. In addition, it has been largely demonstrated that novelty alters endogenous opioid activity.
Objectives: The present study was designed to examine a possible interaction between novelty and naltrexone effects on the behavior of chlordiazepoxide-treated rats in two animal models of anxiety.
Methods: Thirty minutes after acute intraperitoneal treatment with saline or naltrexone and saline or chlordiazepoxide, male Wistar rats were exposed for the first time to the elevated plus maze apparatus or the social interaction arena for the quantification of the percentage of time spent in the open arms or the time of active social interaction, respectively. The effects of naltrexone and/or chlordiazepoxide on the plus maze and the social interaction tests were also evaluated after previous exposure to the respective apparatus.
Results: Naltrexone dose dependently increased the percentage of time spent in the open arms of the elevated plus maze in chlordiazepoxide-treated (5 mg/kg i.p.) rats exposed for the first time to the apparatus. Similarly, naltrexone (5 mg/kg i.p.) increased the time spent in active social interaction by chlordiazepoxide-treated rats exposed to an unfamiliar arena. In both experiments, naltrexone had no effect when administered alone. When both the plus maze and the social interaction tests were conducted after previous exposure to the respective apparatus, naltrexone did not modify the behavior of chlordiazepoxide- or saline-treated rats.
Conclusions: These data suggest that the anxiolytic-like effects of chlordiazepoxide can be modified by opioid mechanisms in novel environments.