Decreased GABA and glutamate concentration in rat brain after treatment with 6-aminonicotinamide

Abstract

The effect of 6-aminonicotinamide (6-AN) on putative amino acid neurotransmitters, namely glutamate, GABA and aspartate was studied on brains of rats treated with this antimetabolite (35 mg/kg i.p.). After 6-AN application the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glucose, glucose 6-phosphate, fructose, glutamate, GABA, aspartate, ammonia, and 6-phosphogluconate. The alterations in the cerebral energy metabolism were found as reported in the literature (increased levels of glucose, glucose 6-phosphate, decreased levels of lactate and pyruvate) and could be interpreted as the result of a reduced glycolytic flux rate. After a prolonged period of 6-AN pretreatment (16-30 h) the GABA and glutamate concentrations were significantly reduced, whereas the level of aspartate remained unchanged. From the result presented the two following conclusions may be drawn: a) The changes in the concentration of neurotransmitters as GABA and glutamate could be responsible for some neurological symptoms produced by 6-AN. b) As 6-AN seems to affect the GABA-shunt it represents a model substance for studying this pathway in the nervous system.