Effects of morphine, ethylketocyclazocine,N-allylnormetazocine and naloxone on locomotor activity in the rabbit

Abstract

Locomotor activity was studied in the rabbit following injections of morphine, ethylketocyclazocine and N-allylnormetazocine. All three drugs produced only depression of activity. The opioid antagonist naloxone antagonized the effects of both morphine and ethylketocyclazocine. Naloxone (0.1 mg/kg) did not antagonize the effects of N-allylnormetazocine. Naloxone alone depressed locomotor activity at doses above 0.3 mg/kg. This effect of naloxone was partially antagonized by 0.1 mg/kg ethylketocyclazocine, but not by 0.1 mg/kg morphine. The GABA agonist muscimol (0.1 and 1.0 mg/kg) also did not antagonize the effect of naloxone on locomotor activity. Finally, amphetamine did not produce a great deal of locomotor activation in the rabbit, which may indicate that increasing activity in the rabbit by drug intervention may be inherently difficult. These results indicate that the opioids have effects in the rabbit that are clearly different from those observed in rodents, where morphine and N-allylnormetazocine have been reported to produce locomotor activation, and naloxone typically has little effect. In addition, the effects of the opioids on locomotor activity were clearly distinguishable from their effects on learning in the rabbit. While morphine and ethylketocyclazocine were approximately equipotent in depressing locomotor activity, morphine is much less potent than ethylketocyclazocine in retarding acquisition of the classically conditioned nictitating membrane response in the rabbit.