Valproate effects on pre-optic GABA release and pituitary LH secretion in the rat

The in vivo effects of the anticonvulsant drug sodium valproate (VPA) on pre-optic gamma-aminobutyric acid (GABA) release and pituitary luteinizing hormone (LH) secretion were studied by perfusing the pre-optic area of unanaesthetized, freely moving ovarectomized rats through push-pull cannulae at a flow-rate of 20 >μl/min with a fraction period of 15 min. Local treatment with 40, 100, 400 and 1600 μg VPA/ml differently affected pre-optic GABA release and pituitary LH secretion concerning mean level, mean pulse amplitude and mean pulse frequency. GABA levels in perfusate were suppressed by local treatment with 40 and 100 μg VPA/ml CSF, respectively, whereas no significant change could be observed at the highest concentration used (1600 μg VPA/ml CSF). Pituitary LH secretion was reduced by pre-optic perfusion with 100 μg VPA/ml CSF with regard to mean plasma level and pulse amplitude but no significant change in pulse frequency could be observed. By raising VPA concentration the effects became more pronounced, and at 1600 μ g VPA/ml CSF there was a marked reduction of LH secretion regarding mean plasma level, amplitude and frequency. In conclusion, the present data put forward our view that the mechanism of action of VPA generates an enhancement of GABAergic transmission different from that involving elevated extracellular GABA.