EFFECT OF MECAMYLAMINE ON THE FATE OF DOPAMINE IN STRIATAL AND MESOLIMBIC AREAS OF RAT BRAIN; INTERACTION WITH MORPHINE AND HALOPERIDOL

Abstract

1 The effects of the nicotinic cholinoceptor blocking drug, mecamylamine (alone or in combination with morphine or haloperidol) were investigated on the striatal homovanillic acid (HVA) concentration and on the α-methyl-p-tyrosine (AMPT)-induced depletion of striatal or mesolimbic dopamine content in the brain of rats. 2 Mecamylamine (2 mg/kg) alone did not alter the striatal HVA concentration, but it reduced the probenecid-induced accumulation of HVA. Mecamylamine pretreatment reduced the morphine-and haloperidol-induced elevation of striatal HVA concentration. Hexamethonium did not alter the striatal HVA concentration when given alone or in probenecid- or morphine-treated rats, whereas pempidine (8 mg/kg) clearly reduced the probenecid-induced accumulation of HVA in the striatum. 3 Mecamylamine (2 and 8 mg/kg) slowed the rate of AMPT-induced depletion of dopamine from the striatum and mesolimbic area both in the brain of control rats and of rats treated with morphine or haloperidol. 4 Mecamylamine slightly prolonged the cataleptic effect of morphine. 5 The results indicate that mecamylamine inhibits the release of dopamine both from the striatal and mesolimbic dopaminergic neurones.