Dose-dependent response of central dopaminergic systems to metoclopramide in mice.
Metoclopramide (5 to 40 mg/kg, i.p.) induces catalepsy and antagonised apomorphine induced cage climbing behaviour in mice. This further indicate its postsynaptic striatal and mesolimbic D 2 dopamine (DA) receptor blocking activity. Metoclopramide at 1.25 and 2.5 mg/kg, i.p. induced stereotyped cage climbing behaviour in mice. Pretreatment with haloperidol and alpha-methyl-p-tyrosine significantly antagonised metoclopramide (1.25 and 2.5 mg/kg)-induced stereotyped cage climbing behaviour. Metoclopramide at these doses induces stereotyped cage climbing behaviour by releasing DA from the mesolimbic dopaminergic neurons with resultant activation of the postsynaptic mesolimbic D 2 DA receptors by the released DA. DA releasing action of metoclopramide (1.25 and 2.5 mg/kg, i.p.) and the subsequent induction of the stereotyped cage climbing behaviour by these doses of metoclopramide is explained on the basis of selective blockade of the presynaptic D 2 DA autoreceptors by these doses of metoclopramide.
Bhosale
K B
KB
Department of Pharmacology, Krishna Institute of Medical Sciences, Karad, India.
Balsara
J J
JJ
Gaonkar
R K
RK
Bhosale
B B
BB
Gupta
S K
SK
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D051379:Mice
D000932:Antiemetics; D018492:Dopamine Antagonists; D008787:Metoclopramide