Effect of mecamylamine on the fate of dopamine in striatal and mesolimbic areas of rat brain; interaction with morphine and haloperidol.
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 alpha-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 concentrations. 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 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.
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D008781:Methyltyrosines / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D051381:Rats
D008781:Methyltyrosines; D008464:Mecamylamine; D009020:Morphine; D006220:Haloperidol; D004298:Dopamine; D006719:Homovanillic Acid