Blockade of tachykinin NK1 receptors attenuates stress-induced rise of extracellular noradrenaline and dopamine in the rat and gerbil medial prefrontal cortex.
Substance P receptor antagonists cause antidepressant- and anxiolytic-like effects in rodents that are thought to involve brain monoamines. In the present study, we examined the effects of the NK1 receptor antagonist GR-205,171 on basal and stress-induced rise of extracellular noradrenaline (NA) and dopamine (DA) in the medial prefrontal cortex (mPFC) of conscious rats and gerbils with the in vivo microdialysis technique. GR-205,171 given intraperitoneally to rats (10 and 30 mg/kg) and gerbils (0.3 and 1 mg/kg) did not affect extracellular NA in either species and increased extracellular DA in rats. Forty minutes of immobilization increased extracellular NA and DA by, respectively, 179% and 188% of baseline values in rats and 222% and 316% of baseline values in gerbils. At 10 mg/kg, GR-205,171 attenuated the stress-induced increase of extracellular NA in the rat. At 30 mg/kg, GR-205,171 suppressed the effect of stress on extracellular DA but had no effect on NA. A lower dose (1 mg/kg) attenuated the stress-induced rise of extracellular NA and DA in the mPFC of gerbils. The results show that blockade of NK1 receptors marginally increased basal extracellular DA in rats but had no effect in gerbils, whereas the stress-induced rise of extracellular NA and DA was markedly attenuated in both species. It is suggested that catecholamines may contribute to the functional effects of GR-205,171.
Renoldi
Giuliano
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Invernizzi
Roberto W
RW
D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D005849:Gerbillinae; D008297:Male; D017551:Microdialysis / Q000379:methods; D064729:Neurokinin-1 Receptor Antagonists; D009638:Norepinephrine / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D012149:Restraint, Physical / Q000379:methods; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D013777:Tetrazoles / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D013777:Tetrazoles; C103207:vofopitant; D004298:Dopamine; D009638:Norepinephrine