Simvastatin reverses the downregulation of dopamine D1 and D2 receptor expression in the prefrontal cortex of 6-hydroxydopamine-induced Parkinsonian rats.
Sprague-Dawley rats with unilateral lesion of the medial forebrain bundle by 6-hydroxydopamine showed marked decrease in the expression of dopamine D1 and D2 receptors in the prefrontal cortex. Simvastatin (10 mg/kg/day for 4 weeks) restored receptor expression to control levels. Given the association of dopaminergic dysfunction in the prefrontal cortex and cognitive deficits in Parkinson's disease, these findings may have implication in the treatment of cognitive decline in advanced Parkinson's disease.
Wang
Q
Q
Department of Pharmacology, Faculty of Medicine, National University of Singapore, 18 Medical Drive, 117597 Singapore.
Wang
P H
PH
McLachlan
C
C
Wong
P T-H
PT
D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D019821:Simvastatin / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D013565:Sympatholytics; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D016627:Oxidopamine; D019821:Simvastatin