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Titolo:
ROLE OF 5-HT IN STRESS, ANXIETY, AND DEPRESSION
Autore:
GRAEFF FG; GUIMARAES FS; DEANDRADE TGCS; DEAKIN JFW;
Indirizzi:
UNIV SAO PAULO,FFCLRP,LAB PSICOFARMACOL BR-14040901 RIBEIRAO PRET SP BRAZIL UNIV SAO PAULO,FMRP,DEPT FARMACOL BR-1404091 RIBEIRAO PRET SP BRAZIL UNIV ESTADUAL PAULISTA,FCLA,DEPT FISIOL BR-19800000 ASSIS SP BRAZIL UNIV MANCHESTER,MANCHESTER ROYAL INFIRM,DEPT PSYCHIAT MANCHESTER M13 9WL LANCS ENGLAND
Titolo Testata:
Pharmacology, biochemistry and behavior
fascicolo: 1, volume: 54, anno: 1996,
pagine: 129 - 141
SICI:
0091-3057(1996)54:1<129:RO5ISA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
LONG-TERM POTENTIATION; SIMULATED PUBLIC SPEAKING; MEDIAN RAPHE NUCLEUS; ELEVATED PLUS-MAZE; BEHAVIORAL CONSEQUENCES; MAJOR DEPRESSION; REPEATED IMMOBILIZATION; DORSAL HIPPOCAMPUS; SEROTONIN FUNCTION; RECEPTOR AGONISTS;
Keywords:
5-HT; DORSAL RAPHE NUCLEUS; MEDIAN RAPHE NUCLEUS; DORSAL HIPPOCAMPUS; ELEVATED T-MAZE; ELEVATED PLUS-MAZE; RESTRAINT STRESS; CONDITIONED SKIN CONDUCTANCE RESPONSES; SIMULATED PUBLIC SPEAKING; STRESS; ANXIETY; DEPRESSION;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Science Citation Index Expanded
Citazioni:
112
Recensione:
Indirizzi per estratti:
Citazione:
F.G. Graeff et al., "ROLE OF 5-HT IN STRESS, ANXIETY, AND DEPRESSION", Pharmacology, biochemistry and behavior, 54(1), 1996, pp. 129-141

Abstract

There are conflicting results on the function of 5-HT in anxiety and depression. To reconcile this evidence, Deakin and Graeff have suggested that the ascending 5-HT pathway that originates in the dorsal raphenucleus (DRN) and innervates the amygdala and frontal cortex facilitates conditioned fear, while the DRN-periventricular pathway innervating the periventricular and periaqueductal gray matter inhibits inborn fight/flight reactions to impending danger, pain, or asphyxia. To studythe role of the DRN 5-HT system in anxiety, we microinjected 8-OH-DPAT into the DRN to inhibit 5 HT release. This treatment impaired inhibitory avoidance (conditioned fear) without affecting one-way escape (unconditioned fear) in the elevated T-maze, a new animal model of anxiety. We also applied three drug treatments that increase 5-HT release from DRN terminals: 1) intra-DRN microinjection of the benzodiazepine inverse agonist FG 4172, 2) intra-DRN microinjection of the excitatory amino acid kainic acid, and 3) intraperitoneal injection of the 5-HT releaser and uptake blocker D-fenfluramine. All treatments enhanced inhibitory avoidance in the T-maze. D-Fenfluramine and intra-DRN kainate also decreased one-way escape. In healthy volunteers, D-fenfluramine and the 5-HT agonist mCPP (mainly 5-HT2C) increased, while the antagonists ritanserin (5-HT2A/(2C)) and SR 46349B (5-HT2A) decreased skin conductance responses to an aversively conditioned stimulus (tone). In addition, D-fenfluramine decreased, whereas ritanserin increased subjective anxiety induced by simulated public speaking, thought to represent unconditioned anxiety. Overall, these results are compatible with the above hypothesis. Deakin and Graeff have suggested that the pathway connecting the median raphe nucleus (MRN) to the dorsal hippocampus promotes resistance to chronic, unavoidable stress. In the present study, we found that 24 h after electrolytic lesion of the rat MRN glandular gastric ulcers occurred, and the immune response to the mitogen concanavalin A was depressed. Seven days after the same lesion, the ulcerogenic effect of restraint was enhanced. Microinjection of 8-OH-DPAT, thenonselective agonist 5-MeO-DMT, or the 5-HT uptake inhibitor zimelidine into the dorsal hippocampus immediately after 2 h of restraint reversed the deficits of open arm exploration in the elevated plus-maze, measured 24 h after restraint. The effect of the two last drugs was antagonized by WAY-100135, a selective 5-HT1A receptor antagonist. These results are compatible with the hypothesis that the MRN-dorsal hippocampus 5-HT system attenuates stress by facilitation of hippocampal 5-HT1A-mediated neurotransmission. Clinical implications of these results are discussed, especially with regard to panic disorder and depression.

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Documento generato il 14/07/20 alle ore 19:42:56