Injection of tachykinins and selective neurokinin receptor ligands into the substantia nigra reticulata increases striatal dopamine and 5-hydroxytryptamine metabolism.
Bilateral injection of endogenous tachykinins (substance P (SP), neurokinin A (NKA)) and selective neurokinin receptor ligands (senktide, [Sar9,Met(O2)11]SP, [MePhe7]NKB) into the substantia nigra reticulata increased striatal dopamine and serotonin metabolism. The increase in dopamine metabolism in the dorsal striatum at a low dose of the substances may be a direct effect on dopamine neurons in the substantia nigra reticulata via NK1 and NK3 receptors. The lack of effect at intermediate doses may be due to inhibitory mechanisms or desensitization. The changes after high doses in the dorsal and ventral striatum may be due to actions on dopaminergic neurons in the substantia nigra as well as in the ventral tegmental area, since there was considerable diffusion from the site of injection. An apparent rapid degradation of injected SP or NKA indicates that N-terminal SP fragments may participate in the SP response. The increased serotonin metabolism that occurs only at a high dose may involve all three neurokinin receptors.
Humpel
C
C
Department of Psychiatry, University Hospital, Innsbruck, Austria.
Saria
A
A
Regoli
D
D
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D013378:Substantia Nigra; D015320:Tachykinins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D010446:Peptide Fragments; D015320:Tachykinins; C054724:senktide; D012701:Serotonin; D013373:Substance P; D004298:Dopamine