Abstract
The effects of naloxone, metenkephalin, and morphine were tested on phencyclidine(PCP)-induced stereotyped behaviors, ataxia, and hyperactivity in the rat. Naloxone (8 mg/kg) significantly decreased stereotypy, ataxia, and hyperactivity across all PCP doses tested (2.0, 4.0, and 6.0 mg/kg). Metenkephalin (40 μg/kg) and morphine (5 and 10 mg/kg) increased ataxia at the 4.0 and 6.0 mg/kg PCP doses. Stereotypy was altered by the opiates in a dose-dependent manner; enhanced by metenkephalin (40 μg/kg) at 2.0 mg/kg and inhibited by metenkephalin (40 μg/kg) and morphine (10 mg/kg) at 4.0 and 6.0 mg/kg PCP. Locomotor activity was increased by morphine (5 mg/kg) at 2 mg/kg PCP. These results suggest an involvement of central opiate receptor mechanisms in the mediation of PCP-induced behaviors in the rat.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adams PM (1980) Interaction of phencyclidine with drugs affecting cholinergic neurotransmission. Neuropharmacology 19:151–153
Adams PM, Beauchamp R, Alston C (1981) Potentiation of apomorphine and d-amphetamine effects by naloxone. Life Sci 28:629–634
Arnsten AT, Segal DS (1979) Naloxone alters locomotion and interaction with environmental stimuli. Life Sci 25:1035–1042
Balster RL, Chait LD (1978) The behavioral effects of phencyclidine in animals. In: Peterson RC, Stillman RC (eds) Phencyclidine (PCP) abuse: An appraisal US Government Printing Office, Washington, DC, pp 53–65
Biggio G, Casu M, Corda MG, DiBello C, Gessa GL (1978) Stimulation of dopamine synthesis in caudate nucleus by intrastriatal enkephalins and antagonism by naloxone. Science 200:552–554
Broekkamp CLE, Phillips AG, Cools AR (1979) Stimulant effects of enkephalin microinjection into the dopaminergic A 10 area. Nature 278:560–562
Browne RG, Segal DS (1980) Behavioral activating effects of opiates and opiate peptides. Biol Psychiatry 15:77–86
Castellani S, Adams PM (1980) Effects of dopaminergic and cholinergic agents on phencyclidine-induced behaviors in rats. Neurosci Abstr 6:311
Castellani S, Adams PM (1981a) Acute and chronic phencyclidine effects on locomotor activity, stereotypy and ataxia in rats. Eur J Pharmacol 73:143–154
Castellani S, Adams PM (1981b) Effects of dopaminergic drugs on phencyclidine-induced behavior in the rat. Neuropharmacology 20:371–374
Chen G, Ensor CR, Russell D, Bohner B (1959) The pharmacology of 1-(l-phenylcyclohexyl) piperidine HCl. J Pharmacol Exp Ther 127:241–250
Cole SO (1978) Brain mechanisms of amphetamine-induced anorexia, locomotion, and stereotypy: A review. Neurosci Biobehav Rev 2:89–100
Costa E, Fratta W, Hong JS, Moroni F, Yang HYT (1978) Interactions between enkephalinergic and other neuronal systems. Adv Biochem Psychopharmacol 18:217–226
Costall B, Fortune DH, Naylor RJ (1976) Biphasic changes in motor behavior following morphine injection into the nucleus accumbens. Br J Pharmacol 57:423
Costall B, Naylor RJ (1974) On catalepsy and catatonia and the predictability of the catalepsy test for neuroleptic activity. Psychopharmacologia 34:233–241
Diamond BI, Borison RL (1978) Enkephalins and nigrostriatal function. Neurology 28:1085–1088
Domino EF (1979) Opiate interactions with cholinergic neurons. Adv Biochem Psychopharmacol 20:339–355
Finnegan KT, Kanner MI, Mettzer HY (1976) Phencyclidine-induced ipsilateral rotational behavior in rats with nigrostriatal lesions and its modulation by dopaminergic and cholinergic agents. Pharmacol Biochem Behav 5:651–660
Garey RE, McQuitty S, Tootle D, Heath RG (1980) The effects of apomorphine and haldol on PCP-induced behavioral and motor abnormalities in the rat. Life Sci 26:277–284
Holtzman SG (1980) Phencyclidine-like discrimination effects of opioids in the rat. J Pharmacol Exp Ther 214:614–619
Itzhak Y, Kalir A, Sarne Y (1981a) On the opioid nature of phencyclidine and its 3-hydroxyl derivative. Eur J Pharmacol 73:229–233
Itzhak Y, Kalir A, Weissman BA, Cohen S (1981b) Receptor binding and antinociceptive properties of phencyclidine opiate-like derivatives. Eur J Pharmacol 72:305–311
Jasinski DR, Shannon HE, Cone EJ, Vaupel DB, Risner ME, McQuinn RL, Su TP, Pickworth WB (1981) Interdisciplinary studies on phencyclidine. In: Domino EF (ed) PCP (phencyclidine): Historical and current perspectives. NPP Books, Ann Arbor, pp 331–400
Joyce EM, Iversen SD (1979) The effect of morphine applied locally to mesencephalic dopamine cell bodies on spontaneous motor activity in the rat. Neurosci Lett 14:207–212
Kornetsky C, Markowitz RA, Esposito RU, (1981) Phencyclidine and naloxone: Effects on sensitivity to aversive and rewarding stimulation in the rat. In: Domino EF (ed) PCP (phencyclidine): Historical and current perspectives. NPP Books, Ann Arbor, pp 321–330
Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW (1977) Endogenous opioid peptide: Multiple agonists and receptors. Nature 267:495–499
Markowitz RA, Kornetsky C (1978) Hypersensitivity to foot-shock following administration of phencyclidine: Interaction with naloxone. Fed Proc 37:619
Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine-and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog J Pharmacol Exp Ther 197:517–532
Meltzer HY, Sturgeon RD, Simonovic M, Fessler RG (1980) Phencyclidine as an indirect dopamine agonist. Psychopharmacol Bull 16:62–65
Menon MK, Clark WG, Vivonia C, (1980) Interaction between phencyclidine (PCP) and GABAergic drugs: Clinical implications. Pharmacol Biochem Behav 12:113–117
Murray TF, Horita A (1979) Phencyclidine-induced stereotyped behavior in rats: Dose-response effects and antagonism by neuroleptics. Life Sci 24:2217–2225
Pert A, Sivit C (1977) Neuroanatomical focus for morphine and enkephalin-induced hypermotility. Nature 265:645–647
Pollard H, Llorens-Cortes C, Schwartz JC (1977) Enkephalin receptors on dopaminergic neurons in rat striatum. Nature 268:745–747
Puri SK, Reddy C, Lal H (1973) Blockade of central dopaminergic receptors by morphine: effect of haloperidol, apomorphine or benztropine. Res Commun Chem Pathol Pharmacol 5:389–401
Schlemmer RE, Jackson JA, Preston KL, Bederka JP, Garver DL, Davis JM (1978) Phencyclidine-induced stereotyped behavior in monkeys: Antagonism by pimozide. Eur J Pharmacol 52:379–384
Shannon H (1981) Evaluation of phencyclidine analogs on the basis of their discriminative stimulus properties in the rat. J Pharmacol Exp Ther 216:543–551
Smith RC, Meltzer HY, Arora RC, Davis JM (1977) Effects of phencyclidine on 3H-catecholamine and 3H-serotonin uptake in synaptosomal preparations from rat brain. Biochem Pharmacol 26:1435–1439
Su TP, Cone EJ, Shannon H, Vaupel DB, (1980) Relative potencies of phencyclidine and analogs in the opiate receptor binding assay: correlation with relative potencies determined in vivo in mouse and rat. Res Commun Subs Abuse 1:85–98
Vincent JP, Kamenka JM, Geneste P, Lazdunski M (1978) Interaction of phencyclidines with the muscarinic and opiate receptors in the central nervous system. Brain Res 152:176–182
Vincent JP, Kartalovski B, Geneste P, Kamenka JM, Lazdunski M (1979) Interaction of phenyclidine (angel dust) with a specific receptor in rat brain membranes. Proc Natl Acad Sci USA 76:4678–4682
Zukin SR, Zukin RS (1979) Specific 3H-phencyclidine binding in rat central nervous system. Proc Natl Acad Sci USA 76:5372–5376
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Castellani, S., Giannini, A.J. & Adams, P.M. Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat. Psychopharmacology 78, 76–80 (1982). https://doi.org/10.1007/BF00470593
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00470593