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, NG-nitro-l-arginine (l-NA, 8 mg kg −1twice 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.