Differential regulation of AP-1 DNA-binding activity by D1 and D2 dopamine receptor antagonists in the rat caudate-putamen and globus pallidus following a unilateral 6-OHDA lesion of the medial forebrain bundle.
The effect of D1 and D2 dopamine receptor antagonists on the DNA-binding activity of the AP-1 transcription factor was studied in the rat caudate-putamen and globus pallidus following a unilateral 6-OHDA lesion of the medial forebrain bundle. In the caudate-putamen, vehicle-treated rats showed increased AP-1 DNA-binding activity, which appeared to be reversed completely by treatment with the D1 receptor antagonist SCH23390 (1 mg kg-1 i.p.) and partially by the D2 antagonist sulpiride (50 mg kg-1 i.p.). In the globus pallidus, vehicle and sulpiride did not induce AP-1, while SCH23390 increased it significantly. This induction was much more prominent in the 6-OHDA-lesioned hemisphere than in the intact hemisphere. The present study suggests that in the caudate-putamen, dopamine-depletion induces long-lasting enhancement of AP-1 DNA-binding activity via activation of D1 receptors and the simultaneous activation of D2 receptors facilitate it. However, in the globus pallidus of the 6-OHDA-lesioned hemisphere, D1 but not D2 antagonism induces AP-1 in certain cell populations which may be distinct from those expressing AP-1 upon stimulation of D2 receptors.
Kashihara
K
K
Department of Neurology, Okayama University Medical School, Japan.
Akiyama
K
K
Ishihara
T
T
Manabe
Y
Y
Abe
K
K
D000818:Animals; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D007839:Functional Laterality; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D004268:DNA-Binding Proteins; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D018808:Transcription Factor AP-1; D016627:Oxidopamine