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An antihypokinesic action of α 2-adrenoceptors upon MPTP-induced behaviour deficits in mice

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The effects of co-administration of either the dopamine precursor, L-Dopa, or the directly-acting, mixed dopamine (DA) agonist, apomorphine, with the α-adrenoceptor agonists, clonidine and guanfacine, upon the motor activity of hypoactive L-Dopa-tolerant MPTP-treated C57 BL/6 mice were measured in four experiments. In each case, MPTP (2 × 40 mg/kg, s.c., separated by a 24-hr interval) was administered eight-to-ten weeks before behavioural testing. It was found that clonidine co-administered with L-Dopa (20 mg/kg) restored motor activity in a dose- and parameter-related manner: locomotion and total activity were restored by the 1 mg/kg dose, rearing behaviour by the 0.3 and 1 mg/kg doses. The restorative effects of clonidine (1 mg/kg), co-administered with L-Dopa, were antagonised completely by pretreatment with yohimbine (1 mg/kg), but not by prazosin (1 mg/kg). Guanfacine (1 mg/kg) co-administered with L-Dopa (20 mg/kg) restored locomotor, but not rearing, behaviour in L-Dopa-tolerant MPTP-treated mice. The antikinesic action of guanfacine was antagonised completely by yohimbine (1 mg/kg), but not prazosin (1 mg/kg). Clonidine (1 or 3 mg/kg) co-administered with apomorphine (0.1, 0.3, 1.0 or 3.0 mg/kg), directly-acting DA agonist, did not restore motor behaviour in the hypokinesic L-Dopa-tolerant MPTP-treated mice. Nor did apomorphine, by itself, affect the motor activity of these animals. Neurochemical analysis indicated marked DA, DOPAC and HVA depletions in the striatum, and to a much lesser extent in the frontal cortex, of MPTP-treated mice. The synergistic antiparkinsonian action of clonidine with L-Dopa, but not apomorphine, in hypokinetic MPTP mice for the restoration of responding to a suprathreshold dose of L-Dopa, to which “wearing-off” had been induced previously, is discussed.

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Received March 4, 2002; accepted July 2, 2002 Published online November 22, 2002

Acknowledgement The administrative and secretarial assistence of Mrs. G. Palm is appreciated.

Authors' address: Dr. T. Archer, Department of Psychology, University of Göteborg, S-40530 Göteborg, Sweden, e-mail: trevor.archer@psy.gu.se

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Archer, T., Fredriksson, A. An antihypokinesic action of α 2-adrenoceptors upon MPTP-induced behaviour deficits in mice. J Neural Transm 110, 183–200 (2003). https://doi.org/10.1007/s00702-002-0777-5

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  • DOI: https://doi.org/10.1007/s00702-002-0777-5

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