Long-term l -Dopa pretreatment of mice: Central receptor subsensitivity or supersensitivity?

Long-term l -Dopa pretreatment of mice: Central receptor subsensitivity or supersensitivity? 213 66 66 1 1 Ruth C. Bailey D. M. Jackson P. U. Bracs Department of Pharmacology University of Sydney 2006 N. S. W. Australia Abstract The effect of acute and repeated treatments with l -Dopa in oral doses of 200 mg/kg plus benserazide (50 mg/kg) was studied using locomotor activity in mice as a model of central catecholaminergic function. Mice pretreated with l -Dopa once daily for 1, 4 or 10 days responded to a challenge dose of l -Dopa (same dose as above) 1 day later with a more pronounced increase in motor activity than vehiclepretreated animals. Dexamphetamine-induced (0.5, 1.0 or 2.0 mg/kg) stimulation was found not to be significantly different in the two pretreatment groups when mice were challenged 1 day after one or four pretreatment doses of l -Dopa. However, a reduced response to dexamphetamine was observed in l -Dopa-pretreated mice (compared to vehicle-treated mice) on withdrawal of the mice from a 10-day l -Dopa pretreatment schedule. One day after one l -Dopa dose, with or without premedication with α-methyl-p-tyrosine (200 mg/kg) plus reserpine (10 mg/kg), mice responded to apomorphine (1.0 mg/kg) with significantly less activity than vehicle-pretreated mice. In contrast, 1 day after ten doses of l -Dopa, there was a shift to the left of the dose-response curve to apomorphine, which did not, however, occur 4 days after withdrawal. Hence, marked dopamine receptor sensitivity changes seem not to be of primary importance for l -Dopa hyperactivity in l -Dopa-pretreated mice. The present study also suggests that dopaminergic changes are not of consequence in the activity induced by dexamphetamine in l -Dopa-pretreated animals. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Long-term l -Dopa pretreatment of mice: Central receptor subsensitivity or supersensitivity?

Psychopharmacology, Volume 66 (1) – Nov 1, 1979

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Publisher
Springer Journals
Copyright
Copyright © 1979 by Springer-Verlag
Subject
Biomedicine; Pharmacology/Toxicology; Psychiatry
ISSN
0033-3158
eISSN
1432-2072
DOI
10.1007/BF00431990
Publisher site
See Article on Publisher Site

Abstract

213 66 66 1 1 Ruth C. Bailey D. M. Jackson P. U. Bracs Department of Pharmacology University of Sydney 2006 N. S. W. Australia Abstract The effect of acute and repeated treatments with l -Dopa in oral doses of 200 mg/kg plus benserazide (50 mg/kg) was studied using locomotor activity in mice as a model of central catecholaminergic function. Mice pretreated with l -Dopa once daily for 1, 4 or 10 days responded to a challenge dose of l -Dopa (same dose as above) 1 day later with a more pronounced increase in motor activity than vehiclepretreated animals. Dexamphetamine-induced (0.5, 1.0 or 2.0 mg/kg) stimulation was found not to be significantly different in the two pretreatment groups when mice were challenged 1 day after one or four pretreatment doses of l -Dopa. However, a reduced response to dexamphetamine was observed in l -Dopa-pretreated mice (compared to vehicle-treated mice) on withdrawal of the mice from a 10-day l -Dopa pretreatment schedule. One day after one l -Dopa dose, with or without premedication with α-methyl-p-tyrosine (200 mg/kg) plus reserpine (10 mg/kg), mice responded to apomorphine (1.0 mg/kg) with significantly less activity than vehicle-pretreated mice. In contrast, 1 day after ten doses of l -Dopa, there was a shift to the left of the dose-response curve to apomorphine, which did not, however, occur 4 days after withdrawal. Hence, marked dopamine receptor sensitivity changes seem not to be of primary importance for l -Dopa hyperactivity in l -Dopa-pretreated mice. The present study also suggests that dopaminergic changes are not of consequence in the activity induced by dexamphetamine in l -Dopa-pretreated animals.

Journal

PsychopharmacologySpringer Journals

Published: Nov 1, 1979

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