Pretreatment with dopamine agonists influences L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat

Lane, Emma Louise ORCID: https://orcid.org/0000-0001-8800-3764 and Dunnett, Stephen Bruce ORCID: https://orcid.org/0000-0003-1826-1578 2010. Pretreatment with dopamine agonists influences L-dopa mediated rotations without affecting abnormal involuntary movements in the 6-OHDA lesioned rat. Behavioural Brain Research 213 (1) , pp. 66-72. 10.1016/j.bbr.2010.04.034

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Abstract

l-dopa induced dyskinesia is a complication of long-term l-dopa administration in patients with Parkinson's disease. This study uses the rodent model of dyskinesia to determine whether prior dopamine agonist treatment causes long-term changes that influence the development of l-dopa mediated behaviours. Rats with unilateral 6-OHDA lesions were injected with dopamine agonists (ropinirole, piribedil bromocriptine, all 1 mg/kg) or saline (0.9%) daily for 21 days. Following a 1-week drug free interval l-dopa was administered for 15 days (10 mg/kg with benserazide 15 mg/kg in saline s.c.). Rotational behaviour and abnormal involuntary movements (AIMs) were recorded at regular intervals. All dopamine agonists induced a contralateral rotational response on day 1, which increased in response to repeated administration but did not by themselves induce overt dyskinesias. On day 1 of l-dopa administration animals pre-treated with piribedil and ropinirole produced a more severe rotational response. In the saline pre-treated group, AIMs developed with repeated l-dopa administration, which was reflected in the increased expression of PPE-B mRNA. There was a trend for the same pattern in the dopamine agonist treated groups but this was non-significant. Therefore, while locomotor sensitivity is altered by the pre-treatment with dopamine agonists, there appears to be no increased risk of developing AIMs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy Biosciences
Uncontrolled Keywords:	Parkinson's disease; 6-OHDA lesioned rat; l-dopa; Dopamine agonist; Dyskinesia
Publisher:	Elsevier
ISSN:	0166-4328
Last Modified:	02 Dec 2022 11:58
URI:	https://orca.cardiff.ac.uk/id/eprint/9149

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