Catecholamine mechanisms in the stimulation of mouse locomotor activity by nitrous oxide and morphine

Abstract

Nitrous oxide, like morphine, produces a significant increase in mouse locomotor activity. This stimulation of locomotor activity is antagonized by the narcotic antagonist naloxone (10 mg/kg). The catecholamine synthesis inhibitor α-methyl-p-tyrosine (300 mg/kg) also significantly reduced the nitrous oxide stimulation of mouse locomotor activity. Administration of naloxone (10 mg/kg) to mice previously treated with α-methyl-p-tyrosine resulted in a further decrease in nitrous oxide stimulated activity levels. Haloperidol (0.08–0.64 mg/kg), a potent dopamine receptor antagonist, dose dependently reduced the activity stimulation resulting from exposure to nitrous oxide. Administration of haloperidol (0.08 mg/kg) in conjunction with naloxone (10 mg/kg) further reduced the nitrous oxide effect. In view of the fact that morphine's activity stimulating effects are reduced by α-methyl-p-tyrosine and haloperidol, the results reported here suggest additional similarities in the pharmacology of morphine and nitrous oxide. The stimulation of mouse locomotor activity produced by nitrous oxide appears to be mediated by both endogenous opioid and catecholamines.