Effects of chronic treatment with the GABA-transaminase inhibitor vigabatrin on exploratory behaviour in rats.
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.
Sherif
F
F
Department of Pharmacology, University for Medical Sciences, Tripoli, Libya.
Oreland
L
L
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin