Effect of clobazam and other benzodiazepines on gamma‐aminobutyric acid (GABA)‐turnover in stressful and nonstressful situations

The relationship between the changes in gamma‐aminobutyric (GABA)‐ergic transmission elicited by the benzodiazepines and the anxiolytic activity and psychomotor deficits they induce was investigated. This was done by administering several anxiolytic and nonanxiolytic compounds to unstressed rats as well as rats exposed to the “open field” apparatus and measuring the resulting changes in GABA‐turnover in five brain regions. The anxiolytics were administered both acutely and chronically and at doses which induced psychomotor deficits as well as at doses which did not. It was found that “open field” exposure (an anxiety paradigm) increased GABA‐turnover in most of the brain areas studied, while anxiolytics tended to reduce GABA‐turnover in most regions even after chronic administration for 5 days. In contrast, nonanxiolytic compounds tended to increase GABA‐turnover, but to a lesser extent than “open field” exposure. In the cerebellum, unlike most of the brain areas studied, GABA‐turnover was reduced only when anxiolytics were given at doses which substantially decreased open field ambulation. On the basis of these data it is concluded that the GABA‐ergic system may mediate both the anxiolytic activity of the benzodiazepines and some of the psychomotor deficits they induce. It is postulated that the lack of psychomotor deficits elicited by clobazam may be attributable to the relatively high doses required to alter GABA‐turnover in the cerebellum as opposed to the brain area(s) which are involved in anxiety.