Abstract
Locomotor activity was studied in the rabbit following injections of morphine, ethylketocyclazocine andN-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 ofN-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 andN-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.
Similar content being viewed by others
References
Browne RG, Segal DS (1980) Behavioral activating effects of opiates and opioid peptides. Biol Psychiatry 15:77–86
Dingledine R, Iversen LL, Breuker E (1978) Naloxone as a GABA antagonist: evidence from iontophoretic, receptor binding and convulsant studies. Eur J Pharmacol 47:19–27
Harris RA (1980) Interactions between narcotic agonists, partial agonists and antagonists evaluated by schedule-controlled behavior. J Pharmacol Exp Ther 213:497–503
Hernandez LL, Powell DA (1983) Naloxone induces multiple effects on aversive Pavlovian conditioning in rabbits. Behav Neurosci 97:478–491
Iwamoto ET (1981) Locomotor activity and antinociception after putativemu, kappa andsigma opioid receptor agonists in the rat: influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217:451–460
Koek W, Slangen JL (1984) Acute effects of naloxone and naltrexone, but lack of delayed effects, on exploratory behavior in the rat. Psychopharmacology 84:383–387
Leslie FM (1987) Methods used for the study of opioid receptors. Pharmacol Rev 39:197–249
Matthews WD, McCafferty GP (1979) Anticonvulsant activity of muscimol against seizures induced by impairment of GABA-mediated neurotransmission. Neuropharmacology 18:855–889
Mauk MD, Warren JT, Thompson RF (1982) Selective, naloxone-reversible morphine depression of learned behavioral and hippocampal responses. Science 216:434–436
Meunier J-C, Zajac J-M (1979) Cerebellar opiate receptors in lagomorphs. Demonstration, characterization and regional distribution. Brain Res 168:311–321
Moerschbaecher JM, Mastropaolo J, Winsauer PJ, Thompson DM (1984) Effects of opioids on accuracy of a fixed-ratio discrimination in monkeys and rats. J Pharmacol Exp Ther 230:541–549
Quirion R, Chicheportiche R, Contreras PC, Johnson KM, Lodge D, Tam SW, Woods JH, Zukin SR (1987) Classification and nomenclature of phencyclidine and sigma receptor sites. Trends Neurosci 10:444–446
Robson LE, Gillam MGC, Kosterlitz HW (1985) Species differences in the concentrations and distribution of opioid binding sites. Eur J Pharmacol 112:65–71
Schindler CW, Harvey JA (1990) The use of classical conditioning procedures in behavioral pharmacology. Drug Dev Res (in press)
Schindler CW, Lamb MR, Gormezano I, Harvey JA (1986) Effects of morphine, ethylketocyclazocine andN-allylnormetazocine on classical conditioning of the rabbit nictitating membrane response. Behav Neurosci 100:647–651
Schindler CW, Gormezano I, Harvey JA (1987) Effects of morphine, ethylketocyclazocine, U-50,488H and naloxone on the acquisition of a classically conditioned response in the rabbit. J Pharmacol Exp Ther 243:1010–1017
Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. Iowa State University Press, Ames, IA, pp 135–171
Tang AH, Collins RJ (1985) Behavioral effects of a novel kappa opioid analgesic, U-50,488, in rats and rhesus monkeys. Psychopharmacology 85:309–314
Tepper P, Woods JH (1978) Changes in locomotor activity and naloxone-induced jumping in mice produced by WIN 35,197-2 (ethylketazocine) and morphine. Psychopharmacology 58:125–129
Thompson RF (1988) The neural basis of basic associative learning of discrete behavioral responses. Trends Neurosci 11:152–155
Von Voigtlander PF, Lahti RA, Ludens JH (1983) U-50,488 H: a selective and structurally novel non-mu (kappa) opioid agonist. J Pharmacol Exp Ther 224:7–12
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schindler, C.W., White, M.F. & Goldberg, S.R. Effects of morphine, ethylketocyclazocine,N-allylnormetazocine and naloxone on locomotor activity in the rabbit. Psychopharmacology 101, 172–177 (1990). https://doi.org/10.1007/BF02244122
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244122