Acute vigabatrin-phenobarbitone-interaction on exploratory behaviour of rats

Abstract

Vigabatrin (gamma-vinyl GABA) is an irreversible inh:bitor of the enzyme GABA-transaminase (GABA-T) which is responsible for the catabolism of the major inhibitory neurotransmitter gamma- aminobutyric acid (GABA) in the brain. Vigabatrin causes a several fold increase in the levels of brain GABA. The current study investigated further the effects of acute treatment with vigabatrin (100 mgl kg, i.p.) & phenobarbitone sodium (20 mg/kg, i.p.)f alone and in combination, in two rat behavioural models of exploratory activity: the elevated plus-maze model of anxiety and the open field test of locomotor activity. A single injection of vigabatrin or phenobarbitone alone, produced anxiolytic effects in the elevated plus-maze test and increased locomotor activity in the open field test. In contrast, after the concomitant administration of both drugs, the anxiolytic effects were no longer produced in the elevated plus-maze. The increased locomotor activity was also diminished in both tests of exploratory behaviour. These results shed light on the GABA hypothesis of anxiety, insofar as the increased availability of GABA, resulting from either GABA-T inhibition (vigabatrin) or facilitation of GABA-mediated chloride channels (phenobarbitone), seems to result in an increased emotional reactivity which, however, subsequently disappears during combined treatment.