Chronic infusion of a melanocortin receptor agonist modulates dopamine receptor binding in the rat brain.
Previous studies have shown that melanocortin peptides have facilitatory effects on dopaminergic neurotransmission. In the present study we tested the hypothesis that chronic exposure to melanocortin receptor agonists causes a prolonged release of dopamine resulting in changes in the expression of dopamine receptor subtypes. Using an autoradiographic approach we found that a 2 week intracerebroventricular infusion of the melanocortin receptor agonist melanotan-II induced changes in dopamine D(1)-like and D(2)-like receptor binding in several regions of the rat brain. D(1)-like receptor binding was increased in the nucleus accumbens and the caudate putamen, but reduced in the substantia nigra (reticular part), whereas D(2)-like receptor binding was reduced in the caudate putamen, but increased in the periaqueductal grey, substantia nigra (compact part) and the ventral tegmental area. These data suggest that chronic infusion of a melanocortin receptor agonist alters the activity of dopaminergic neurons in the ventral tegmental area and substantia nigra, and support the hypothesis that melanocortin peptides may regulate the activity of central dopamine neurons.
Lindblom
Jonas
J
Department of Pharmaceutical Pharmacology, University of Uppsala, Uppsala 75124, Sweden.
Kask
Ants
A
Hägg
Erik
E
Härmark
Linda
L
Bergström
Lena
L
Wikberg
Jarl
J
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D015918:Infusion Pumps, Implantable; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015854:Up-Regulation; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology*
D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C081720:alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-; D000521:alpha-MSH