Respiratory and locomotor stimulation by low doses of dermorphin, a mu1 receptor-mediated effect

The selective opioid mu receptor agonist dermorphin increased the locomotor activity of rats dose dependently at 10 to 100 pmol/kg i.c.v. Respiratory rate, relative tidal volume and respiratory minute volume also increased unrelated to changes in locomotor activity. Higher doses, on the other hand, produced catalepsy and respiratory depression. Pretreatment of the rats with the mu1-selective antagonist naloxonazine (10 mg/kg i.v.) blocked the stimulant locomotor and respiratory effects of low doses of dermorphin (10-100 pmol/kg), but potentiated the respiratory depressant effect of a high dose (10 nmol/kg) of dermorphin. The selective benzodiazepine antagonist flumazenil (5 mg/kg), which has been shown previously to antagonize catalepsy and respiratory depression produced by relatively high doses of dermorphin, did not antagonize the respiratory or locomotor stimulant effect of dermorphin. The data suggest that mu1-opioid receptors are responsible for the low dose stimulant effects of dermorphin on locomotor activity and respiration whereas mu2 receptors mediate the respiratory depressant effect of dermorphin.