Abstract
Drugs of abuse, such as phencyclidine (PCP), methamphetamine (METH), and cocaine (COC) are known to affect several behaviors in rats, such as motor activity, stereotypy, and circling. In this study, we evaluated whether these drugs produce circling preferences in the presence or absence of unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the caudate nucleus. Adult male CD rats were lesioned with 10 μg 6-OHDA/site. Animals were dosed with PCP (15 mg/kg, ip), its congener, (+) MK-801 (0.15 mg/kg, ip), METH (2 mg/kg, ip), COC (60 mg/kg, ip), or apomorphine (0.2 mg/kg, ip). circling preference was recorded in control and lesioned rats for 2 h before animals were sacrificed to determine monoamine levels by HPLC/EC. In control animals, administration of these drugs produced 60–70% left circling. In, lesioned animals, these drugs produced 78–90% ipsilateral (toward the lesion) circling, except apomorphine, which produced 60–80% contralateral (away from the lesion) circling. Dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations significantly decreased ipsilaterally in lesioned caudate nucleus (CN) and substantia nigra (SN). However, no significant changes were observed in nucleus accumbens (NA) and olfactory tubercles (OT). These data demonstrate that drugs of abuse like PCP, its congener (+) MK-801, METH, and COC produce a greater preference to turn toward the left than the right, a finding similar to that found in human psychosis. Since 6-OHDA lesions enhanced the circling bias and depleted DA and its metabolites DOPAC and HVA, it also suggests that the dopaminergic system may be involved in the circling behavior.
Similar content being viewed by others
References
Ali S. F., Newport G. D., and Bracha H. S. (1992) Phencyclidine, (+)-MK-801 and TCP-induced circling preference: correlation with monoamine levels in selected regions of the rat brain.Soc. Neurosci. Abstr. 449, 11.
Ali S. F., David S., and Newport G. D. (1993a) Agerelated susceptibility to MPTP-induced neurotoxicity in mice.Neurotoxicology 14, 29–34.
Ali S. F., Burt R. L., Newport G. D., and Bracha H. S. (1993b) Drug-induced circling preference in rats: correlation with monoamine levels.Teratology 463, NBTS32.
Ali S. F., Newport G. D., and Bracha H. S. (1994a) Phencyclidine and (+) MK-801-induced circling preference: correlation with monoamine levels in striatum of the rat brain.Neurotox. Teratol. 16, 335–342.
Ali S. F., Newport G. D., Holson R. R., Slikker W., Jr., and Bowyer J. F. (1994b) Low environmental temperature or pharmacologic agents that produce hypothermia decrease methamphetamine neurotoxicity in mice.Brain Res. 658, 33–38.
Arnt. J. and Hyttel J. (1985) Differential involvement of dopamine D1 and D3 receptors in the circling behavior induced by apomorphine, SKF-38393 pergolide and LY 171555 in 6-hydroxydopaminelesioned rats.Psychopharmacology 85, 346–352.
Bracha H. S. (1989) Is there a right-hemi-hypredopaminergic psychosis?.Schizophrenia Res. 2, 317–324.
Bracha H. S. (1987) Asymmetric rotational (circling) behavior, a dopamine-related asymmetry: preliminary finding in unmedicated and never-medicated schizophrenic patients.Biol. Psychiatr. 22, 995–1003.
Bracha H. S., Livingston R. L., Clotheir J., Linington B. B., and Karson C. N. (1993) Correlation of severity of psychiatric patient’s delusions with right hemispatial inattention (left turning behavior).Am. J. Psychiatr. 150, 330–332.
Christie J. and Crow T. J. (1971) Turning behavior as an index of the action of amphetamines and ephedrine on central dopamine-containing neurons.Br. J. Pharmacol. 43, 658–667.
Domino E. F. and Luby E. D. (1981) Abnormal mental states induced by phencyclidine as a model for schizophrenia, inPCP (Phenyclidine): Historical and Current Perspectives (Domino E. F., ed.), NPP Books, Ann Arbor, MI, pp. 401–418.
Duncan D. B. (1955) Multiple range and multiple F-test.Biometrics 11, 1–10.
Early T. S., Reiman E. M., Raichel M. E., and Spitzinagel E. L. (1987) Left globus pallidus abnormality in nerver-medicated patients with schizophrenia.Proc. Natl. Acad. Sci. USA 84, 561–564.
Early T. S., Posner M. I., Reiman E. M., and Raichle M. E. (1989) Hyperactivity of the striato-pallidal projection, Part I: lower level of theory.Psychiatr. Dev. 2, 1075–1081.
Ellison G., Eison M. S., Huberman H. S., and Daniel F. (1978) Long-term changes in dopaminergic innveration of caudate nucleus after continuous amphetamine administration.Science 201, 276–278.
Fessler R. G., Sturgeon R. D., and Meltzer H. Y. (1979) Phencyclidine-induced ipsilateral rotation in rats with unilateral 6-hydroxydopamine-induced lesions of the substantia nigra.Life Sci. 24, 1281–1288.
George F. R. and Ritz M. C. (1990) Cocaine produces locomotor stimulation in SS-mice but not in LS-mice: relationship to dopaminergic function.Psychopharmacology 101, 18–22.
Glick S. D. and Cox R. D. (1978) Nocturnal rotation in normal rats: correlation with amphetamine-induced rotation and effects of nigrostriatal lesions.Brain Res. 150, 149–161.
Glick S. D., Hinds P. A., and Shapiro R. M. (1983) Cocaine-induced rotation, sex-dependent differences between left and right sided rats.Science 221, 777.
Glick S. D., Meibach R. C., Cox R. D., and Maayanii S. (1980) Phencyclidine-induced rotation and hippocampal modulation of nigrostriatal asymmetry.Brain Res. 196, 99–107.
Glick S. D. and Ross D. A. (1981) Lateralization of function in the rat brain mechanisms may be operative in humans.Trends Neurosci. 4, 198, 199.
Greenberg B. D. and Segal D. S. (1985) Acute and chronic behavioral interaction between phencyclidine (PCP) and amphetamine: evidence for a dopaminergic role is some PCP-induced behaviors.Pharmacol. Biochem. Behav. 23, 99–105.
Gur R. E., Gur R. C., Skolnick B. E., Caroff S., Obrist W. D., Resnick S., and Reivich M. (1985) Brain function in psychiatric disorders: III. regional cerebral blood flow in unmedicated schizophrenics.Arch. Gen. Psychiatr. 42, 329–334.
Herrear-Marschwitz M. and Ungerstedt U. (1985) Effect of the dopamine D1 antagonist SCH 23390 on rotational behavior induced by apomorphine and pergolide in 6-hydroxydopamine denervated rats.Eur. J. Pharmacol. 109, 349–354.
Hiramatsu M., Cho A. K., and Nabeshima T. (1989) Comparison of the behavioral and biochemical effects of the NMDA receptor antagonist, MK-801 and phencyclidine.,Eur. J. Pharmacol. 166, 359–366.
Iversan S. D., Singh L., Oles R. J., Preston C., and Tricklebank M. D. (1988) Psychopharmacological profile of theN-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, inSigma and Phencyclidine-Like Compounds as Molecular Probe in Biology (Domino E. F. and Kamenka J. M., eds.), NPP Books, Ann Arbor, MI, p. 373.
Jaffe J. H. (1990) Drug addiction and drug abuse, inThe Pharmacological Basis of Therapeutics (Gilman A. G., Rall T. H., Nies A. S., and Taylor eds.), Pergamon, p. 550.
Javitt D. C. and Zukin S. R. (1991) Recent advances in the Phencyclidine model of schizophrenia.Am. J. Psychiatr. 148, 1301–1308.
Jerussi T. P. and Glick S. D. (1974) Amphetamine induced rotation in rats without lesionsNeuropharmacology 13, 283–286.
Karlsson G., Jason A. L., and Vigouret J. M. (1988) Dopamine-D1-receptor and dopamine-D2-receptor interaction in turning behavior induced by dopamine agonist in 6-hydroxydopamine-lesioned rats.Neurosci. Lett. 88, 69–74.
Kanner M., Finnega K., and Meltzer H. Y. (1975) Dopaminergic effects of phencyclidine in rats with nigrostriatal lesions.Psychopharmacol. Commun. 114, 393–401.
Kogan F. J., Nichols W. K., and Gibb J. W. (1976) Influence of methamphetamine on nigral and striatal tyrosine hydroxylase activity and on striatal dopamine levels.Eur. J. Pharmacol. 36, 363–371.
Luby E. D., Gottileb J. S., Cohen B. D., Rosenbaum G., and Domino E. F. (1962) Model psychosis and schizophrenia.Am. J. Psychiatr. 119, 61–67.
Marwaha J. (1982) Candidate mechanisms underlying PCP-induced psychosis: an electrophysiological, behavioral and biochemical study.Biol. Psychiatr. 17, 155–198.
Nabeshima T. (1986) Effects of phencyclidine the drug induces psychosis on the central nervous system.J. Pharma. Soc. Jpn. 106, 351–370.
Nabeshima T., Yamaguchi K., Hiramatsu M., Amano M., Furukawa H., and Kameyama T. (1984) Sertogenergic involvement in phencyclidine-induced behaviors.Pharmacol. Biochem. Behav. 21, 401–408.
Paxinos G. and Watson C. (1986)The Rat Brain in Stereotaxic Coordinates. Academic, New York.
Reith M. E. A., Sershen H., and Lajtha A. (1982) Binding of3H-labeled cocaine in mouse brain-kinetics and saturability.J. Receptor Res. 2, 233–243.
Scalzo F. M. and Holson R. R. (1992) The ontogeny of behavioral sensitization to phencyclidine.Neurotoxcol., Teratol. 14, 7–14.
Seiden L. S., Fischman M. W., and Schuster C. R. (1975) Long-term methamphetamine induced changes in brain catecholamines in tolerance rhesus monkeys.Drug Alcohol Depend. 1, 215–219.
Thadani U. and Whitsett T. L. (1991) Beta- adrenergic blockers and intermittent claudication-time for reappraisal.Arch. Int. Med. 151, 1705–1707.
Ungerstedt V. and Arbuthnot G. W. (1970) Quantitative recording of behavior in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system.Brain Res. 24, 485–493.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ali, S.F., Kordsmeier, K.J. & Gough, B. Drug-induced circling preference in rats. Mol Neurobiol 11, 145–154 (1995). https://doi.org/10.1007/BF02740691
Issue Date:
DOI: https://doi.org/10.1007/BF02740691