Document Detail

Drug-induced circling preference in rats. Correlation with monoamine levels.
MedLine Citation:
PMID:  8561958     Owner:  NLM     Status:  MEDLINE    
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 micrograms 6-OHDA/site. Animals were dosed with PCP (15 mg/kg, ip) its congener (+) MK-801 (0.15 mg/kp, ip), METH (2 mg/kg, ip) COC (60 mg/kp, 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 determined 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.
S F Ali; K J Kordsmeier; B Gough
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Molecular neurobiology     Volume:  11     ISSN:  0893-7648     ISO Abbreviation:  Mol. Neurobiol.     Publication Date:    1995 Aug-Dec
Date Detail:
Created Date:  1996-03-07     Completed Date:  1996-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8900963     Medline TA:  Mol Neurobiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  145-54     Citation Subset:  IM    
Neurochemistry Laboratory, National Center for Toxicological Research/FDA, Jefferson, AR 72079-9502, USA.
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MeSH Terms
3,4-Dihydroxyphenylacetic Acid / metabolism
Apomorphine / pharmacology*
Biogenic Amines / metabolism*
Brain / drug effects,  metabolism,  physiology*
Caudate Nucleus / drug effects,  metabolism*
Chromatography, High Pressure Liquid
Cocaine / pharmacology*
Dopamine / metabolism
Homovanillic Acid / metabolism
Methamphetamine / pharmacology*
Motor Activity / drug effects*
Organ Specificity
Oxidopamine / toxicity
Phencyclidine / pharmacology*
Psychotic Disorders
Rats, Sprague-Dawley
Reference Values
Stereotyped Behavior / drug effects*
Substantia Nigra / drug effects,  metabolism*
Reg. No./Substance:
0/Biogenic Amines; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 1199-18-4/Oxidopamine; 306-08-1/Homovanillic Acid; 50-36-2/Cocaine; 537-46-2/Methamphetamine; 58-00-4/Apomorphine; 77-10-1/Phencyclidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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