Antinociceptive and antitussive effects of morphine in the DA-bg/bg (Beige) rat

Antinociceptive and antitussive effects of morphine were studied in DA-bg/bg (Beige) rats. Intraperitoneal administration of morphine(10 mg/kg) produced a marked antinociceptive effect, in the tail-flick test, in Beige rats and DA rats, a progenitor strain rats. There was no significant difference in the peak antinociceptive effect of morphine between Beige rats and DA rats. The antinociceptive effect of morphine in both Beige rats and DA rats was significantly reduced following pretreatment with a low dose (0.3 mg/kg, i.p.) of naloxone or naltrexonazine (1 mg/kg, s.c.), a selective mu(1)-opioid receptor antagonist. Morphine suppressed coughs dose dependently at doses between 0.3-3 mg/kg, i.p., in Beige rats and between 0.1-1.0 mg/kg, i.p., in DA rats. The antitussive potency of morphine in Beige rats was less than that in DA rats. The antitussive effect of morphine was significantly antagonized by pretreatment with naloxone (0.3 mg/kg, i.p.) in both Beige rats and DA rats. However, pretreatment with naltrexonazine (1 mg/kg, s.c.), a selective mu(1)-opioid receptor antagonist, had no effect on the antitussive effect of morphine. These results suggest that Beige rats are hyporesponsive to the mu(2)-opioid receptor-mediated antitussive effect, but not to the mu(1)-opioid receptor-mediated antinociceptive effect.