Neurokinin-3 receptors modulate dopamine cell function and alter the effects of 6-hydroxydopamine.
Neurokinin-3 receptor expression within rat midbrain dopamine neurons was demonstrated using a combination of in situ hybridization and receptor autoradiographic techniques. Continuous intranigral infusion of the neurokinin-3 receptor agonist senktide selectively increased striatal dopamine metabolism over a period of several days, followed by apparent development of tolerance. In contrast, in animals with moderate unilateral 6-hydroxydopamine-induced lesions of nigrostriatal dopamine cells, intranigral senktide infusion increased dopamine turnover in the surviving dopamine neurons and reduced functional dopamine asymmetry (reflected by spontaneous rotations) over the 2-week period tested. Thus nigral neurokinin receptors can modulate normal dopamine cell activity and may provide a therapeutic target in the treatment of Parkinson's disease.
Bannon
M J
MJ
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA.
Brownschidle
L A
LA
Tian
Y
Y
Whitty
C J
CJ
Poosch
M S
MS
D'sa
C
C
Moody
C A
CA
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D004298:Dopamine / Q000378:metabolism*; D015870:Gene Expression; D017403:In Situ Hybridization; D008297:Male; D008636:Mesencephalon / Q000378:metabolism / Q000502:physiology*; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018042:Receptors, Neurokinin-3 / Q000235:genetics*; D013997:Time Factors
D018042:Receptors, Neurokinin-3; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D004298:Dopamine