Inhibitory effect of a selective kappa receptor agonist, U-50, 488H, on methamphetamine-elicited ipsilateral circling behavior in rats with unilateral nigral lesions.
The present study was designed to investigate the effect of U-50, 488H, a highly selective kappa opioid agonist, on ipsilateral and contralateral circling behavior induced by methamphetamine and by apomorphine, respectively. U-50, 488H (3.2-10 mg/kg IP) by itself failed to induce either ipsilateral or contralateral circling in rats with unilateral nigral lesions produced by an injection of 6-hydroxydopamine. U-50, 488H produced a significant dose-dependent inhibition of methamphetamine (1.0 mg/kg SC)-elicited ipsilateral circling. However, it had no effect on contralateral circling induced by apomorphine (0.5 mg/kg SC). The present results indicate that U-50, 488H presynaptically inhibits the release of dopamine in the rat striatum.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yamamoto
T
T
Ueki
S
S
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000502:physiology*; D013997:Time Factors
D000700:Analgesics; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D008694:Methamphetamine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D001058:Apomorphine