Effects of chronic treatment with the GABA-transaminase inhibitor vigabatrin on exploratory behaviour in rats

Abstract

Vigabatrin (gamma-vinyl GABA, GVG) is an irreversible inhibitor of the enzyme GABA-transaminase (GABA-T). GABA-T is the enzyme responsible for the catabolism of the major inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the mammalian brain. Previously, a single administration of vigabatrin at a dose of 50 mg/kg was found to produce an anxiolytic-like effect on exploratory behaviour in rats and a decrease in the locomotor activity, 2 and 4 h after the injection and, presently, 24 h after the injection. Using an elevated plus-maze and open field tests, we investigated whether or not chronic administration of vigabatrin at the same dose (50 mg/kg/day, i.p.) for 14 and 28 days induces tolerance with regard to these effects. The anxiolytic-like effect of vigabatrin was found to persist in the elevated plus-maze test, as was the case with diazepam (5 mg/kg/day, i.p.), 24 h after the last injection. However, in the plus-maze and open field tests, the effects of vigabatrin and diazepam on the general locomotor activity were not found to be decreased.