Behavioral Involvement of Central Dopamine D1 and D2 Receptors in 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

The Japanese Journal of Pharmacology

Eiji Mizuta²  Tetsuo Akai¹  Masaki Ozawa¹  Motonori Yamaguchi¹  Sadako Kuno² 

[1] Research Department, Institute of Pharma Research, Development and Medical Science, Nihon Schering K.K.;Department of Neurology, Center for Neurological Diseases, Utano National Hospital

关键词: Parkinsonism;    Dopamine D1;    receptor;    Dopamine D2 receptor;    MPTP;    Monkey;   

DOI  :  10.1254/jjp.67.117

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(22)Cited-By(13)To clarify the roles of dopamine D1, and D2 receptors in behavioral symptoms of Parkinson''s disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D1, antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D1-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D1, or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D1, and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.

【 授权许可】

Unknown