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Titolo:
Sustained blockade of neurokinin-1 receptors enhances serotonin neurotransmission
Autore:
Haddjeri, N; Blier, P;
Indirizzi:
Univ Florida, Dept Psychol, McKnight Brain Inst, Gainesville, FL 32610 USAUniv Florida Gainesville FL USA 32610 ain Inst, Gainesville, FL 32610 USA
Titolo Testata:
BIOLOGICAL PSYCHIATRY
fascicolo: 3, volume: 50, anno: 2001,
pagine: 191 - 199
SICI:
0006-3223(20010801)50:3<191:SBONRE>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYPOTHALAMIC 5-HT1A RECEPTORS; DORSAL HORN NEURONS; SUBSTANCE-P; RAT-BRAIN; IN-VIVO; NEUROENDOCRINE RESPONSES; NOCICEPTIVE RESPONSES; ANTIDEPRESSANT DRUGS; TONIC ACTIVATION; LIMBIC REGIONS;
Keywords:
depression; anxiety; substance P; dorsal raphe; dorsal hippocarnpus; CP-96,345;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Blier, P Univ Florida, Dept Psychol, McKnight Brain Inst, POB 100256, Gainesville, FL 32610 USA Univ Florida POB 100256 Gainesville FL USA 32610 le, FL 32610 USA
Citazione:
N. Haddjeri e P. Blier, "Sustained blockade of neurokinin-1 receptors enhances serotonin neurotransmission", BIOL PSYCHI, 50(3), 2001, pp. 191-199

Abstract

Background: Antagonists of neurokinin-1 (NK1) receptors, through which substance P acts, have been proposed to belong to a new class of antidepressants with a unique mode of action. It was postulated that they exert this putative therapeutic effect independently of the serotonin (5-HT) neurons. Methods: The aim of the present study was to assess, using in vivo electrophysiological paradigms, the effects of sustained administration of the nonpeptidic NK1 antagonist CP-96,345 on the firing activity of rat dorsal raphe 5-HT neurons, the responsiveness of pre- and postsynaptic 5-HT1A receptors, and overall 5-HT neurotransmission in the hippocampus. Results: Both short- and long-term treatments with CP96,345 significantly increased the spontaneous firing activin, of dorsal raphe 5-HT neurons, andthis increase was associated with an attenuation of somatodendritic 5-HT1Aautoreceptor responsiveness. In contrast, the inactive enantiomer of CP-96,345 at NK, receptors, CP-96,344, did not alter these parameters after short-term administration. Because 5-HT1A receptor activation inhibits the firing activity of dorsal hippocampus CA(3) pyramidal neurons, the degree of disinhibition produced by the selective 5-HT1A receptor antagonist WAY 100635was determined to assess the net change in 5-HT neurotransmission. Intravenous injection of WAY 100635 did not disinhibit CA3 pyramidal neuron firingin rats given saline, CP-96,345 for 2 days, or CP-96,344 for 14 days, but produced a significant enhancement of firing in rats treated with CP-96,345for 2 weeks. Therefore, only long-term treatment with CP-96,345 enhanced the tonic activation of postsynaptic 5-HT1A receptors. Conclusions: Similar to all other major types of antidepressant treatments, these data indicate that substance P antagonists might alleviate anxiety and major depression, at least in part, by enhancing the degree of activation of some 5-HT receptors in the forebrain. (C) 2001 Society of Biological Psychiatry.

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Documento generato il 31/03/20 alle ore 15:59:26