IN-VIVO EFFECTS OF CARBAMAZEPINE AND HALOPERIDOL ON GABA NEUROTRANSMISSION AND LH-SECRETION

The in vivo effects of carbamazepine (CBZ) and haloperidol (HAL) on th e neuroendocrine pre-optico-pituitary feedback system were studied by local application of the drugs, in single and in combination mode, thr ough a push-pull cannula into the pre-optic area and measurement of th eir local effects on gamma-aminobutyric acid (GABA) and their distant effects on a subsequent biological response: the pituitary luteinizing hormone (LH) secretion. The perfusion flow rate was 20 mu l cerebrosp inal fluid (CSF)/min; the fraction period was 15 min. Perfusion with 8 mu g CBZ/ml CSF caused a reduction in pre-optic pre-synaptic GABA rel ease and, concomitantly, a suppression of plasma LH levels. Applicatio n of 100 ng HAL/ml CSF also caused a reduction in GABA release, but no significant change in plasma LH levels. During the combined perfusion , the effects of CBZ and HAL did not add up with regard to the pre-opt ic GABA release. These results suggest that both drugs interact with t he GABA system, but they may involve two different mechanisms of actio n. Due to the known inhibitory role of pre-optic GABA in pituitary LH secretion, it can be inferred that, in contrast to HAL, CBZ increases post-synaptic GABAergic transmission.