Naltrexone potentiates the anxiolytic effects of chlordiazepoxide in rats exposed to novel environments

Rationale: Both novelty and naloxone have been reported to modify the anxio lytic-like effect of benzodiazepines in the elevated plus maze. In addition , it has been largely demonstrated that novelty alters endogenous opioid ac tivity. Objectives: The present study was designed to examine a possible in teraction between novelty and naltrexone effects on the behavior of chlordi azepoxide-treated rats in two animal models of anxiety. Methods: Thirty min utes after acute intraperitoneal treatment with saline or naltrexone and sa line 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 tim e 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. Result s: Naltrexone dose dependently increased the percentage of time spent in th e 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, naltrexo ne (5 mg/kg i.p.) increased the time spent in active social interaction by chlordiazepoxide-treated rats exposed to an unfamiliar arena. In both exper iments, naltrexone had no effect when administered alone. When both the plu s maze and the social interaction tests were conducted after previous expos ure to the respective apparatus, naltrexone did not modify the behavior of chlordiazepoxide- or saline-treated rats. Conclusions: These data suggest t hat the anxiolytic-like effects of chlordiazepoxide can be modified by opio id mechanisms in navel environments.