The selective neurokinin (NK)(1) antagonist, GR205,171, stereospecifically enhances mesocortical dopaminergic transmission in the rat: a combined dialysis and electrophysiological study.
Upon acute, systemic administration, the selective, non-peptidergic NK(1) receptor antagonist, GR205,171, dose-dependently enhanced the firing rate of ventrotegmental dopaminergic neurones. Dialysate levels of dopamine were increased in the frontal cortex, but not in the striatum and nucleus accumbens, of conscious rats. These actions were stereospecific in that its less-active isomer, GR226,206, was ineffective. Further, they were selective for dopaminergic pathways inasmuch as the firing rate of dorsal raphe serotonergic neurones and dialysate levels of serotonin were unaffected by GR205,171. Activation of mesocortical dopaminergic pathways may be involved in the influence of NK(1) antagonists upon mood.
Lejeune
Françoise
F
Institut de Recherches Servier, Centre de Recherches de Croissy, Psychopharmacology Department, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, Paris, France.
Gobert
Alain
A
Millan
Mark J
MJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007536:Isomerism; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D000932:Antiemetics; D018491:Dopamine Agonists; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D017366:Serotonin Receptor Agonists; D013777:Tetrazoles; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C103207:vofopitant; D001058:Apomorphine; D004298:Dopamine