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Titolo:
Influence of 5-HT1A receptors on central noradrenergic activity: microdialysis studies using (+/-)-MDL 73005EF and its enantiomers
Autore:
Hajos-Korcsok, E; McQuade, R; Sharp, T;
Indirizzi:
Univ Oxford, Radcliffe Infirm, Dept Clin Pharmacol, Oxford OX2 6HE, England Univ Oxford Oxford England OX2 6HE in Pharmacol, Oxford OX2 6HE, England
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 2, volume: 38, anno: 1999,
pagine: 299 - 306
SICI:
0028-3908(199902)38:2<299:IO5ROC>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRAIN MICRODIALYSIS; ANTAGONIST PROPERTIES; DORSAL RAPHE; MDL 73005EF; RAT; AGONISTS; RELEASE; INVIVO; LIGAND; 5-HYDROXYTRYPTAMINE;
Keywords:
5-hydroxytryptamine; serotonin; 5-HT1A receptors; MDL 73005EF; noradrenaline; microdialysis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Sharp, T Univ2Oxford, Radcliffe Infirm, Dept Clin Pharmacol, Woodstock Rd,Oxford OX Univ Oxford Woodstock Rd Oxford England OX2 6HE ck Rd, Oxford OX
Citazione:
E. Hajos-Korcsok et al., "Influence of 5-HT1A receptors on central noradrenergic activity: microdialysis studies using (+/-)-MDL 73005EF and its enantiomers", NEUROPHARM, 38(2), 1999, pp. 299-306

Abstract

Recent studies indicate that 5-HT1A receptor agonists stimulate noradrenaline release in the brain. Here we investigate the mechanism underlying the increase in extracellular noradrenaline induced by (+/-)-MDL 73005EF, a weak 5-HT1A receptor agonist. Extracellular noradrenaline was measured in the hippocampus of the awake rat using microdialysis. (+/-)-MDL 73005EF (0.1, 1and 5 mg/kg s.c.) caused a dose-related increase in noradrenaline. The active S(-)- enantiomer of MDL 73005EF (1 mg/kg s.c.) also increased noradrenaline whereas the inactive R(+)- enantiomer (1 mg/kg s.c.) did not. Measurements of extracellular 5-HT in hippocampus of anaesthetised rats confirmed that the 5-HT1A receptor agonist action of (+)-MDL 73005EF resides in the S(-)- enantiomer. Thus, S(-)-MDL 73005EF (0.3 and 1 mg/kg s.c.) markedly decreased 5-HT, whereas R(+)-MDL 73005EF (1 mg/kg s.c.) did not. The noradrenaline response to (+/-)-MDL 73005EF (1 mg/kg s.c.) was significantly blocked by the selective 5-HT1A receptor antagonist, WAY 100635 (1 but not 0.3 mg/kg s.c). The noradrenaline response to (+/-)-MDL 73005EF (1 mg/kg s.c.) was not modified by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine. Intra-hippocampal application of(+/-)-MDL 73005EF (10 mu M in perfusion medium) did not increase noradrenaline. Although (+/-)-MDL 73005EF has moderate affinity for dopamine D-2 binding sites, the dopamine D-2 receptor antagonist, remoxipride (1 mg/kg s.c.) did not increase noradrenaline. In conclusion, our data suggest that (+/-)-MDL 73005EF increases noradrenaline release in rat hippocampus through activation of 5HT(1A) receptors that appear to be located postsynaptically. These data are discussed in relation to the antidepressant/anxiolytic effects of 5-HT1A agonists. (C) 1999 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 19:05:16