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Indian J Exp Biol ; 2007 Aug; 45(8): 712-9
Artigo em Inglês | IMSEAR | ID: sea-62437

RESUMO

Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.


Assuntos
Animais , Antitussígenos/farmacologia , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Dextroanfetamina/farmacologia , Dextrometorfano/farmacologia , Dopamina/metabolismo , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacocinética , Inibidores da Captação de Dopamina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Haloperidol/toxicidade , Masculino , Ratos , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Estereotipado/efeitos dos fármacos
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