The ventral tegmental area as a putative target for tachykinins in cardiovascular regulation.
Tachykinin receptor agonists and antagonists were microinjected into the ventral tegmental area (VTA) to study the relative participation of the three tachykinin receptors in cardiovascular regulation in freely behaving rat. Selective agonists (1-100 pmol) for NK1 ([Sar9, Met (O2)11]SP), NK2 ([beta-Ala8]NKA (4-10)) and NK3 (senktide) receptors evoked increases in blood pressure, heart rate (HR) along with behavioural manifestations (face washing, sniffing, head scratching, rearing, wet dog shake). At 1 pmol, NK1 and NK3 agonists did not affect behaviour and blood pressure but only HR. Tachykinin agonists-induced cardiovascular responses were selectively and reversibly blocked by the prior injection of antagonists for NK1 receptors (LY 303870 ((R)-1-[N-(2-methoxybenzyl)acetylamino]-3-(1H-indol-3-yl)-2-[N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino]propane), 5 nmol), NK2 receptors (SR 48968 ([(S)-N-methyl-N-[4-acetylamino-4-phenylpiperidino-2-(3,4-dichlorophenyl)butyl]benzamide]), 250 pmol) and NK3 receptors (SB 235375 ((-)-(S)-N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide), 25 nmol). With the exception of the NK2 agonist, most behavioural effects were also blocked by antagonists. Tachykinin agonists-induced cardiovascular responses were inhibited by intravenous (i.v.) treatments with antagonists for D1 dopamine receptor (SCH23390, 0.2 mg kg(-1)) and beta1-adrenoceptor (atenolol, 5 mg kg(-1)) but not for D2 dopamine receptor (raclopride, 0.16 mg kg(-1)). Behavioural responses were blocked by SCH23390 only. The present study provides the first pharmacological evidence that the three tachykinin receptors in the rat VTA can affect the autonomic control of blood pressure and HR by increasing midbrain dopaminergic transmission. This mechanism may be involved in the coordination of behavioural and cardiovascular responses to stress and noxious stimulation.
Deschamps
Kathleen
K
Department of Physiology, Faculty of Medicine, Université de Montréal, CP 6128, Succursale Centre-ville, Montréal, Québec, Canada H3C 3J7.
Couture
Réjean
R
D000085:Acetates / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
C096759:1-(N-(2-methoxybenzyl)acetylamino)-3-(1H-indol-3-yl)-2-(N-(2-(4-(piperidin-1-yl)piperidin-1-yl)acetyl)amino)propane; D000085:Acetates; D000319:Adrenergic beta-Antagonists; D001549:Benzamides; D001552:Benzazepines; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; C444647:N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011804:Quinolines; D017447:Receptors, Dopamine D1; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; C054724:senktide; C062618:substance P, Sar(9)-Met(O2)(11)-; C064218:neurokinin A (4-10), beta-Ala(8)-; D013373:Substance P; D018698:Glutamic Acid; D001262:Atenolol; C073839:SR 48968; D015288:Neurokinin A