Intranigral antagonism of neurokinin 1 and 3 receptors reduces intrastriatal dopamine D1 receptor-stimulated locomotion in the rat.
Stimulation of striatal dopamine (DA) D1 receptors increases the activity of the direct striatonigral pathway resulting in movement. While GABA has long been considered the primary effector of this pathway, co-released tachykinin peptides and their respective nigral tachykinin receptors are also in position to influence movement. Therefore, the present studies determined to what extent nigral tachykinin receptor subtypes contribute to striatal D1-mediated locomotion. Adult male Sprague-Dawley rats bearing chronic cannulae in the dorsal striatum and/or substantia nigra (SN) were tested for locomotor responses to various drug infusions. Unilateral intranigral infusions of the neurokinin-1 (NK1) antagonist LY306740 (0 and 50 nmol) but not the neurokinin-3 (NK3) antagonist SR142801 (0 and 50 nmol) led to ipsilateral rotations. Bilateral intrastriatal infusions of the full D1 agonist SKF 82958 (0, 1.2 and 12.0 nmol) dose-dependently increased locomotion. Prior bilateral intranigral infusions of LY306740 or SR142801 (0, 5.0 and 50 nmol) dose-dependently attenuated locomotor activity induced by intrastriatal SKF 82958 (12.0 nmol). These findings indicate that NK1, but not NK3, receptors within the SN may be tonically stimulated. However, activation of both nigral NK1 and NK3 receptors appears to be required for increased locomotion in response to striatal D1 receptor stimulation.
Bishop
Christopher
C
Department of Anatomy and Cell Biology, Wayne State University, School of Medicine, Detroit, 540 E. Canfield, MI 48201, USA. cbishop@med.wayne.edu
Walker
Paul D
PD
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018042:Receptors, Neurokinin-3 / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
D001552:Benzazepines; D017447:Receptors, Dopamine D1; D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; C071262:SK&F 82958