delta-Opioid modulation of striatal dopaminergic activity in mice

Mu- and delta-opioid subtype receptor antagonists were tested in the mouse for their effects on vertical climbing activity, an index of striatal dopaminergic activity. The selective delta-opioid antagonist ICI 154 129 (I/l) by itself enhanced vertical climbing activity in a dose-related manner, whereas the mu-opioid antagonist naloxone by itself was inactive on climbing behavior. Naloxone increased the climbing-stimulant effect of I/l. Unstimulated vertical climbing activity was reduced, and all opioid-antagonist enhancement of climbing behavior was antagonized, by the competitive dopamine antagonist haloperidol in dose-related fashion. The observed motor-enhancement effect of a selective delta-opioid receptor antagonist is the first demonstration of physiologically-significant tonic activity on a central opioid receptor. Our observations suggest that I/l may be useful clinically in striatal dopamine-deficient disease conditions such as parkinsonism.