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Drug-induced circling preference in rats

Correlation with monoamine levels

  • Proceedings of the Symposium Cellular and Molecular Mechanisms of Drugs of Abuse Cocaine and Methamphetamine held in Nice, France, August 19–20, 1993
  • Published:
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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.

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Authors and Affiliations

  1. Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, 72079-9502, Jefferson, AR

    S. F. Ali & K. J. Kordsmeier

  2. Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research/FDA, 72079-9502, Jefferson, AR

    B. Gough

  3. Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, 72205, Little Rock, AR

    S. F. Ali

  4. Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, 72205, Little Rock, AR

    S. F. Ali

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  3. B. Gough
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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

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