Behavioural effects of L-DOPA and bromocriptine in a rat model of Parkinson's disease

Behavioural effects of L-DOPA and bromocriptine in a rat model of Parkinson's disease

Field: Disorders of the nervous system

Authors: Lundblad, Martin
Winkler, Christian
Andersson, Malin
Wierup, Nils
Kirik, Deniz
Cenci, M. Angela

Address of presenting
author: Martin Lundblad
Wallenberg Neurocenter, avd. f. Neurobiologi, inst. f. fysiologiska vetenskaper
Sölvegatan 17, S-223 62 Lund, Sweden
Hämtställe 57

E-mail: Martin.Lundblad@mphy.lu.se

Phone: 046 222 05 55

Fax: 046 222 05 61

Text of abstract: In order to obtain a rat model of Parkinson’s disease, unilateral dopamine-denervating lesions were performed by either intrastriatal (n=18) or intramesencephalic (n=18) injections of 6-hydroxydopamine. At 4 weeks post-lesion, three well-matched groups of rats received single daily i.p. injections of either vehicle, methyl L-DOPA (6 mg/kg), or bromocriptine (3.5 mg/kg) for three weeks. During this period the rats were subjected to three types of tests on alternate days: (i) scoring of L-DOPA-induced abnormal involuntary movements (AIMs); (ii) recording of rotation; (iii) independent use of the forelimbs to support body weight (cylinder test).
L-dopa and bromocriptine produced a similar improvement in the cylinder test. However, during the course of the treatment the rats in the L-DOPA group developed increasingly severe AIMs, bromocriptine-treated rats showed a very low incidence and severity of AIMs, while vehicle-injected rats did not exhibit any AIMs. In the rotation test, the rate and diameter of turning were significantly larger in the bromocriptine group compared to the L-DOPA group. In the second part of the study the effects of non-dopaminergic agents, which have been shown to reduce dyskinesia in MPTP-monkeys and/or patients, were tested. The L-DOPA-induced AIMs scores were significantly reduced by naloxone (-19%; 4-8 mg/kg), yohimbine (-91%, 10 mg/kg; -23%, 1 mg/kg), 5-MDOT (-37%, 2 mg/kg), clozapine (- 22%, 4 mg/kg; -28%, 8 mg/kg) and amantadine (-51%; 40 mg/kg).
The present data validate our rat AIMs scale as a feasible model of L-DOPA-induced dyskinesia, corroborate the cylinder test as a suitable method to assess akinesia in rats, and show that the dynamics of rotation are very different after administration of bromocriptine or L-DOPA.

Keywords: Parkinson's disease, L-dopa induced dyskinesia, rat model, 6-hydroxydopamine

	Behavioural effects of L-DOPA and bromocriptine in a rat model of Parkinson's disease
Field:	Disorders of the nervous system
Authors:	Lundblad, Martin Winkler, Christian Andersson, Malin Wierup, Nils Kirik, Deniz Cenci, M. Angela
Address of presenting author:	Martin Lundblad Wallenberg Neurocenter, avd. f. Neurobiologi, inst. f. fysiologiska vetenskaper Sölvegatan 17, S-223 62 Lund, Sweden Hämtställe 57
E-mail:	Martin.Lundblad@mphy.lu.se
Phone:	046 222 05 55
Fax:	046 222 05 61
Text of abstract:	In order to obtain a rat model of Parkinson’s disease, unilateral dopamine-denervating lesions were performed by either intrastriatal (n=18) or intramesencephalic (n=18) injections of 6-hydroxydopamine. At 4 weeks post-lesion, three well-matched groups of rats received single daily i.p. injections of either vehicle, methyl L-DOPA (6 mg/kg), or bromocriptine (3.5 mg/kg) for three weeks. During this period the rats were subjected to three types of tests on alternate days: (i) scoring of L-DOPA-induced abnormal involuntary movements (AIMs); (ii) recording of rotation; (iii) independent use of the forelimbs to support body weight (cylinder test). L-dopa and bromocriptine produced a similar improvement in the cylinder test. However, during the course of the treatment the rats in the L-DOPA group developed increasingly severe AIMs, bromocriptine-treated rats showed a very low incidence and severity of AIMs, while vehicle-injected rats did not exhibit any AIMs. In the rotation test, the rate and diameter of turning were significantly larger in the bromocriptine group compared to the L-DOPA group. In the second part of the study the effects of non-dopaminergic agents, which have been shown to reduce dyskinesia in MPTP-monkeys and/or patients, were tested. The L-DOPA-induced AIMs scores were significantly reduced by naloxone (-19%; 4-8 mg/kg), yohimbine (-91%, 10 mg/kg; -23%, 1 mg/kg), 5-MDOT (-37%, 2 mg/kg), clozapine (- 22%, 4 mg/kg; -28%, 8 mg/kg) and amantadine (-51%; 40 mg/kg). The present data validate our rat AIMs scale as a feasible model of L-DOPA-induced dyskinesia, corroborate the cylinder test as a suitable method to assess akinesia in rats, and show that the dynamics of rotation are very different after administration of bromocriptine or L-DOPA.

Keywords:	Parkinson's disease, L-dopa induced dyskinesia, rat model, 6-hydroxydopamine

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Created 2000-03-14

Department of Physiological Sciences, Lund University

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