Alterations in regional brain GABA concentration and turnover during pregnancy

Abstract

During pregnancy, mice are more susceptible to flurothyl-induced seizures than are nonpregnant control mice. The potential role of brain GABA in mediating this behavior was examined in the present study. GABA concentrations in the cerebellum, hippocampus, striatum, midbrain, and cortex from individual control, pregnant (days 17–18) and delivery-day Heterogeneous Stock mice were assayed using a fluorometric method. Turnover of GABA was assessed by inhibiting metabolism with aminooxyacetic acid and measuring GABA accumulation over the next 2 h. Steady-state GABA concentrations decreased significantly from control in all brain regions during pregnancy. Reductions in GABA concentrations were approximately 25–30% in the affected regions. At parturition, GABA concentrations in the cerebellum and cortex returned to control levels, but hippocampal, striatal, and midbrain GABA levels remained significantly depressed. All the indices of GABA turnover-first-order rate constant, half-life, initial rate of synthesis, and turnover rate (product of first-order rate constant and initial concentration)-showed a significant reduction in pregnancy, which was continued through the time of delivery in all brain regions except the hippocampus. Half-life values for GABA increased nearly fourfold in the cerebellum and cortex. These results show that there is a significant alteration in GABAergic systems during pregnancy and parturition. We suggest that the reduction in GABA turnover is a compensatory anticonvulsant mechanism to offset the inherent seizure susceptibility brought about by the reduced level of the major inhibitory neurotransmitter in the brain.