Effects of dextromethorphan on dopamine dependent behaviours in rats.
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.
Gaikwad
R V
RV
Department of Pharmacology, Krishna Institute of Medical Sciences, Karad 415 110, India.
Gaonkar
R K
RK
Jadhav
S A
SA
Thorat
V M
VM
Jadhav
J H
JH
Balsara
J J
JJ
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology* / Q000633:toxicity; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced*; D003913:Dextroamphetamine / Q000494:pharmacology; D003915:Dextromethorphan / Q000494:pharmacology* / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000633:toxicity; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013239:Stereotyped Behavior / Q000187:drug effects*
D000996:Antitussive Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011954:Receptors, Dopamine; D016194:Receptors, N-Methyl-D-Aspartate; D003915:Dextromethorphan; D006220:Haloperidol; D001058:Apomorphine; D003913:Dextroamphetamine; D004298:Dopamine