BICUCULLINE MICROINJECTIONS INTO THE VENTRAL TEGMENTAL AREA OF THE RAT - ALTERATION OF SELF-STIMULATION THRESHOLDS AND OF CYTOCHROME-OXIDASE ACTIVITY IN THE BRAIN

Abuse of drugs that potentiate GABAergic neurotransmission, namely ben zodiazepines, is difficult to understand because this potentiation sho uld elicit, among other effects, a decrease in activity within the mes olimbic system. Abuse of benzodiazepines is difficult to understand si nce the opposite, namely an increase in mesolimbic activity, has been implicated in drug abuse as well as in the rewarding effect of direct mesolimbic stimulation. In order to evaluate how the activity of the m esolimbic system depends on mesolimbic GABAergic influence, a GABA, re ceptor antagonist, bicuculline methiodide, was unilaterally injected i nto the ventral tegmental area and its effect on self-stimulation thre sholds derived from stimulations applied to the same area was evaluate d. Microinjection of 15, 20 and 30 ng increased the stimulation thresh old. This decrease in stimulation efficiency lasted no more than 15 mi n after which baseline levels were obtained. Such a decrease is parado xical considering that the manipulation should have released the ventr al tegmentum from a tonic inhibitory influence. The metabolic conseque nces of repeated injections of 30 ng bicuculline were furthermore eval uated by cytochrome oxidase histochemistry. The staining was found to be weak around the injection site and dense in the ipsilateral nucleus accumbens. Release of a tonic GABAergic inhibition added to some cyto toxic damage probably resulted in an increased metabolic activity of t his system. The presently reported paradoxical response of the ventral tegmentum and mesolimbic system to a GABAergic challenge may account for the paradoxical relationship between some behavioral properties of the mesolimbic system and GABAergic drugs.