6-OHDA-induced lesion of the nigrostriatal dopaminergic neurons potentiates the inhibitory effect of 7-OHDPAT, a selective D3 agonist, on acetylcholine release during striatal microdialysis in conscious rats.
Using striatal microdialysis, we attempted to clarify whether or not locally infused 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), a selective D3 agonist, modulates the basal acetylcholine (ACh) release in conscious rats sham-operated and lesioned with 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. In the sham-operated rats, 7-OHDPAT at 1 microM decreased ACh release by 19% of control. In the 6-OHDA-lesioned rats, 7-OHDPAT (0.1-10 microM) decreased ACh release in a concentration-dependent manner. The decrease of 37% of control was seen at 1 microM 2 weeks after the lesion. The 7-OHDPAT (1 microM)-induced decrease was completely antagonized by 1 microM (-)-sulpiride, a D2 and D3 antagonist, while (-)-sulpiride at 1 microM alone failed to alter ACh release. There may exist intrastriatal D3 receptors to inhibit ACh release, and supersensitization is evident in a 6-OHDA-lesioned rat Parkinson's model.
Sato
K
K
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Ueda
H
H
Okumura
F
F
Misu
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology*; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D017551:Microdialysis; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; C493595:Drd3 protein, rat; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D013469:Sulpiride; D016627:Oxidopamine; D001058:Apomorphine; D000109:Acetylcholine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin