The effect of 3-mercaptopropionate,an inhibitor of glutamate decarboxylase,on the levels of GABA and other amino acids,and on presynaptic inhibition in the rat cuneate nucleus

Rats were anaesthetized with urethane and treated with the reversible competitive glutamate decarboxylase (GAD) inhibitor 3-mercaptopropionate (3-MP: 150mg/kg) in order to lower the endogenous levels of GABA. Within 15min GAD activity and GABA levels had decreased by about 50 and 30% respectively in the region of the caudal medulla containing the dorsal column nuclei (den). The decreased GABA levels were subsequently maintained for at least 45 min. In unanaesthetized animals, running fits and tonic clonic convulsions occur within 15 min coincident with the rapid fall in GABA levels. Urethane appeared to protect against such convulsant activity without itself altering GABA levels or the decrease in levels produced by 3-MP. Taurine and glycine levels were unaffected by 3-MP, glutamine levels rose progressively, glutamate levels rose transiently, aspartate and serine levels fell progressively and alanine levels fell sharply within 5 min, subsequently rising to the pre-treatment level. The level of presynaptic inhibition in the dcn was also decreased by 3-MP, as assessed from the size of the surface recorded P-wave produced by supramaximal, electrical stimulation of the ipsilateral forepaw. The observed similarity in time course between the alteration of GABA levels and the decrease in presynaptic inhibition supports previous studies suggesting that GABA is the transmitter mediating synaptic inhibition in the den.