Intrastriatal injection of opioid receptor agonists inhibits apomorphine-induced behavior in 6-hydroxydopamine-treated mice.
The effects of intrastriatal (i.st.) injections of mu-, delta-, and kappa-selective opioid receptor agonists on the augmentation of apomorphine-induced behaviors were determined in 6-hydroxydopamine-treated mice by using multidimensional behavioral analyses. 6-Hydroxydopamine (16 mu g/mu l, i.st.) was unilaterally injected into the striatum 30 min after pretreatment with desipramine (25 mg/kg, s.c). Mice were tested 14 days after injection of 6-hydroxydopamine. Apomorphine (0.5 mg/kg, s.c.) produced a marked increase in linear locomotion, contralateral circling and/or rearing behavior in 6-hydroxydopamine- but not vehicle-treated mice. Although the mu-selective opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) (0.1 and 0.3 ng, i.st.) or the kappa-selective opioid agonist dynorphin A-(1-13) (0.1 and 0.3 mu g, i.st.) did not produce any significant effects on behavior, these peptides had an inhibitory effect on the apomorphine (0.5 mg/kg, s.c.)-induced increase in behavioral responses such as linear locomotion, contralateral circling and/or rearing behavior in 6-hydroxydopamine-treated mice. The inhibitory effects of DAMGO (0.3 ng, i.st.) and dynorphin A-(1-13) (0.3 mu g, i.st.) were fully reversed by selective opioid receptor antagonists such as beta-funaltrexamine (5 mu g, i.c.v.) and (--)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorph an (Mr2266) (10 mg/kg, s.c.), respectively. In contrast, the delta-selective opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.03, 0.1 or 0.3 mu g, i.st.) had no marked effects on the apomorphine (0.5 mg/kg, s.c.)-induced behavior in 6-hydroxydopamine-treated mice. These results suggest that the stimulation of mu- and kappa- but not delta-opioid receptors plays an inhibitory role in the behavioral augmentation induced by the activation of postsynaptic dopamine receptors in the striatum sensitized with 6-hydroxydopamine.
Toyoshi
T
T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Ukai
M
M
Kameyama
T
T
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D016627:Oxidopamine; D010446:Peptide Fragments / Q000494:pharmacology; D011957:Receptors, Opioid / Q000819:agonists*
D004745:Enkephalins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; C024524:beta-funaltrexamine; C026843:dynorphin (1-13); D004399:Dynorphins; D020881:Enkephalin, D-Penicillamine (2,5)-; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine