Effect of acute administration of antidepressant maprotiline on regional levels of inhibitory and excitatory neurotransmitter amino acids in rat brain

ABSTRACT

Groups of rats were injected with increasing doses of the antidepressant, maprotiline [0.0, 2.5, 12.5 and 25.0 mg/kg ip]. The dose range corresponded to average human therapeutic dose, loading dose and overdosage levels. The concentrations of glycine [Gly], gamma aminobutyric acid [GABA], taurin [Tau], aspartate [Asp] and glutamate [Glu] in the cortex, hippocampus, midbrain and the cerebellum were determined 2 hr after dosing using gas liquid chromatography. Maprotiline increased the hippocampal level of GABA, the cerebellar levels of ASP and Glu, but otherwise decreased the levels of the estimated amino acids in the different areas tested. The rank order of the response correlated with loci of action of the antidepressants and is in harmony with adverse reactions of overdosing of maprotiline. Changes in brain amino acids were suggested to be involved in the mechanism of action as well as neurotoxic effects of maprotiline probably through modulation of the firing rates of noradrenergic nerve fibers