A linear relationship between lamotrigine and GABA in cerebrospinal fluid

ABSTRACT: Theγ-amino butyric acid (GABA)-mediated neurotransmission is useful in treat-ing conditions like anxiety, sleep disturbances, depression and bipolar disorders. The aim ofthe present study is to supply evidence about neurochemical effects of acute lamotriginetreatment on GABA and L-glutamic acid levels in the cerebrospinal fluid of Wistar Albino ratsand the involvement of cholinergic system. The day after the placement of concentric micro-dialysis probes into the lateral ventricles of rats, microdialysis experiments were performedin conscious rat model. The rats either received intraperitoneal injections of physiologicalsaline or 20 mg/kg lamotrigine. For assessing the cholinergic involvement 0.5 mg/kg phys-ostigmine or 2 mg/kg atropine sulfate pre-treatments were given prior to lamotrigine injec-tion. GABA, L-glutamic acid and lamotrigine concentrations in the dialysates were analyzedusing High Performance Liquid Chromatography. Saline produced no change in GABA orL-glutamic acid levels, but lamotrigine treatment significantly elevated GABA concentrations(p<0.05). Pre-treatment with physostigmine or atropine sulfate did not affect either GABA or L-glutamic acid levels siginificantly. Physostigmine or atropine sulfate pre-treatments did not affect the lamotrigine-induced GABA levels. The results may imply that lamotrigine-induced GABA plays a role in the pharmacological effects of lamotrigine where a linear relationship exists between lamotrigine and GABA. However, central cholinergic system fails to affect lamotrigine-induced GABA release.