Intrastriatal injection of opioid receptor agonists inhibits apomorphine-induced behavior in 6-hydroxydopamine-treated mice

Abstract

The effects of intrastriatal (i.st.) injections of μ-, δ- and κ-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 μg/μl, 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 μ-selective opioid receptor agonist [ d-Ala 2, N-Me-Phe 4,Gly 5-ol]enkephalin (DAMGO) (0.1 and 0.3 ng, i.st.) or the κ-selective opioid agonist dynorphin A-(1–13) (0.1 and 0.3 μg, 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 μg, i.st.) were fully reversed by selective opioid receptor antagonists such as β-funaltrexamine (5 μg, i.c.v.) and (−)-(1 R,5 R,9 R)-5,9-diethyl-2-(3-furyl-methyl)-2′-hydroxy-6,7-benzomorphan (Mr2266) (10 mg/kg, s.c.), respectively. In contrast, the δ-selective opioid receptor agonist [ d-Pen 2, l-Pen 5]enkephalin (DPLPE) (0.03, 0.1 or 0.3 μg, 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 μ- and κ- but not δ-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.