Postdrug retention of diazepam’s effects on habituation to a novel environment in an animal model of anxiety

Abstract

In two experiments it was demonstrated that diazepam can have habituation-facilitating effects that will be retained beyond the termination of drug action. Rats given multiple exposures to a novel plus maze 30 min after an injection of diazepam (2.0 mg/kg) on each occasion explored the “open” (exposed) arms of the maze more than animals injected with saline or yohimbine hydrochloride did. All groups exhibited equivalent rates of increase in this activity over repeated trials in the maze—behavior that was interpreted to reflect habituation to the environment and, in particular, habituation to the somewhat aversive open arms. When shifted to saline injections in later trials, the animals with diazepam experience retained their relatively higher level of open-arm exploration for as long as 56 days after their last diazepam injection. In a third experiment, animals were confined to the open arms of the maze on five occasions following either a diazepam or a saline injection and were then tested drug-free in the complete maze on subsequent trials. Here the diazepam-experienced animals did not differ from the saline controls. The forced exposure to the open arms, although unequally stressful to the diazepam- and saline-injected animals as indicated by their different fecal bolus counts, yielded comparable, high levels of open-arm exploration in both groups of subjects once they were permitted access to the entire maze. © 1992, Psychonomic Society, Inc.. All rights reserved.