NEUROCHEMICAL ACTIONS OF GABAPENTIN IN MOUSE-BRAIN

Gabapentin (GBP) is a recently licenced antiepileptic drug whose mode of action remains to be fully elucidated. The following studies were d esigned to investigate the effects of GBP on several gamma-aminobutyri c acid (GABA) related neurochemical parameters in mouse brain. GBP (0- 75 mg/kg) was administered by intraperitoneal injection either as a si ngle dose or twice daily for 8 days. Animals were sacrificed 4 h after the final administration and their brains removed and analysed for co ncentrations of GABA, glutamate and glutamine and the activities of GA BA-transaminase (GABA-T) and glutamic acid decarboxylase (GAD). Single dose GBP increased brain GABA-T activity and glutamine concentration but was without effect on GAD activity or the concentrations of GABA a nd glutamate. Following repeated treatment with GBP, brain GABA-T acti vity was consistently decreased and there was also a decrease in brain glutamate concentration. Repeated drug treatment was without effect o n the activity of GAD or on the concentrations of GABA and glutamine. These results suggest that GBP has effects on the GABAergic system whi ch may contribute to its antiepileptic and/or neuroprotective actions. (C) 1997 Elsevier Science B.V.