Role of nitric oxide in catalepsy and hyperthermia in morphine-dependent rats.

Abstract The possible involvement of nitric oxide (NO) in morphine-induced catalepsy and hyperthermia was studied in morphine-dependent rats. Four days repeated injection regimen was used to induce morphine dependence, which was assessed by naloxone challenge (0.5 mg kg −1 , s.c.). Pretreatment of rats with the NO synthase inhibitor, N G -nitro- l -arginine ( l -NA, 8 mg kg −1 twice daily, i.p.) potentiated the cataleptic response of morphine as shown by a rightward shift in the morphine-log dose–response curve. Prior treatment of rats with the NO precursor, l -arginine (200 mg kg −1 , twice daily, i.p.) abolished the potent effect of l -NA and restored the cataleptic scores to levels similar to those of morphine-dependent rats. The same dose of l -NA significantly blocked morphine-induced hyperthermia at the dose levels of morphine (15–105 mg kg −1 ) and this effect was reversed by l -arginine. These data provide the first experimental evidence that NO is involved in morphine induced catalepsy and hyperthermia and demonstrated that blockade of NO synthesis may suggest a dangerous interaction with opioids in the control of motor function.