In vivo effects of carbamazepine and haloperidol on GABA neurotransmission and LH secretion

Abstract

The in vivo effects of carbamazepine (CBZ) and haloperidol (HAL) on the neuroendocrine pre-optico-pituitary feedback system were studied by local application of the drugs, in single and in combination mode, through a push-pull cannula into the pre-optic area and measurement of their local effects on γ-aminobutyric acid (GABA) and their distant effects on a subsequent biological response: the pituitary luteinizing hormone (LH) secretion. The perfusion flow rate was 20 μl cerebrospinal fluid (CSF)/min; the fraction period was 15 min. Perfusion with 8 μg CBZ/ml CSF caused a reduction in pre-optic pre-synaptic GABA release and, concomitantly, a suppression of plasma LH levels. Application 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-optic GABA release. These results suggest that both drugs interact with the GABA system, but they may involve two different mechanisms of action. 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.

Toxicometabolomics and Biotransformation Product Elucidation in Single Zebrafish Embryos Exposed to Carbamazepine from Environmentally-Relevant to Morphologically Altering Doses

“…The amino acid aspartate is also notable since it connects glycerophospholipid metabolism, purine metabolism, histidine metabolism, and pyrimidine metabolism (see Figure ). This connection also entails the neurotransmitter GABA. , Although it is not its primary anticonvulsant MoA, there is evidence demonstrating that CBZ interacts with the release of GABA in neurons and potentiation of the GABA A receptor. − The potentiation of the receptor over time would explain the decrease in GABA in the highest doses in our dataset (see Figure ). A nonlinear GABA response in ZF embryos exposed to CBZ at concentrations comparable to the lower doses of this study (1–100 μg/L) was previously reported .…”