The anxiogenic drug yohimbine is a reinforcer in male and female rats

Abstract

The indole alkaloid yohimbine is an anxiogenic drug that activates stress-responsive systems in the brain. However, because yohimbine also elicits approach behaviors, this study employed male and female Sprague-Dawley rats to explore its potential reinforcing effects. Thus, it was first determined if intravenous (IV) infusions of yohimbine (0.25 mg/kg/infusion) could maintain lever pressing, whether intake could be modulated by dose/infusion, and if lever pressing would persist in the absence of yohimbine or yohimbine-paired cues. Next, to assess yohimbine’s effect on memory consolidation, 0.3, 1.25 or 3 mg/kg yohimbine was administered post-training using an object recognition memory task. Finally, place conditioning assessed whether doses of yohimbine that elevate blood serum corticosterone levels (1.25 or 3 mg/kg) could elicit a conditioned place preference. It was found that both sexes acquired yohimbine IV self-administration, that intake was modulated by dose/infusion, and that lever pressing persisted during extinction and in the absence of the yohimbine-paired cue. As well, post-training injections of 1.25 mg/kg yohimbine enhanced consolidation of object memory, and 1.25 and 3 mg/kg elevated corticosterone levels and elicited a place preference in both sexes. Finally, in behavioral tests of psychomotor functions, acute yohimbine increased lever pressing for a visual cue and elevated locomotor activity. These findings reveal a profile of yohimbine’s behavioral effects that is consistent with that of psychostimulant reinforcing drugs.