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Titolo:
THE 5-HT(1A) RECEPTOR SELECTIVE LIGANDS, (R)-8-OH-DPAT AND (S)-UH-301, DIFFERENTIALLY AFFECT THE ACTIVITY OF MIDBRAIN DOPAMINE NEURONS
Autore:
ARBORELIUS L; CHERGUI K; MURASE S; NOMIKOS GG; HOOK BB; CHOUVET G; HACKSELL U; SVENSSON TH;
Indirizzi:
KAROLINSKA INST,DEPT PHARMACOL,POB 60400 S-10401 STOCKHOLM 60 SWEDEN KAROLINSKA INST,DEPT PHARMACOL,POB 60400 S-10401 STOCKHOLM 60 SWEDEN CTR HOSP LYON SUD,INSERM,U171 F-69310 PIERRE BENITE FRANCE CTR HOSP LYON SUD,CNRS,URA 1195 F-69310 PIERRE BENITE FRANCE MIE UNIV,SCH MED,DEPT PHYSIOL TSU MIE 514 JAPAN UNIV UPPSALA,DEPT ORGAN PHARMACEUT CHEM S-75123 UPPSALA SWEDEN
Titolo Testata:
Naunyn-Schmiedeberg's archives of pharmacology
fascicolo: 4, volume: 347, anno: 1993,
pagine: 353 - 362
SICI:
0028-1298(1993)347:4<353:T5RSL(>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
VENTRAL TEGMENTAL AREA; CENTRAL NERVOUS-SYSTEM; DORSAL RAPHE NUCLEUS; SUBSTANTIA NIGRA; RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; ELECTROPHYSIOLOGICAL EVIDENCE; INTERFASCICULAR NUCLEUS; SEROTONIN RECEPTORS; BINDING-SITES;
Keywords:
5-HT(1A); DOPAMINE; ELECTROPHYSIOLOGY; VENTRAL TEGMENTAL AREA; SUBSTANTIA-NIGRA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
67
Recensione:
Indirizzi per estratti:
Citazione:
L. Arborelius et al., "THE 5-HT(1A) RECEPTOR SELECTIVE LIGANDS, (R)-8-OH-DPAT AND (S)-UH-301, DIFFERENTIALLY AFFECT THE ACTIVITY OF MIDBRAIN DOPAMINE NEURONS", Naunyn-Schmiedeberg's archives of pharmacology, 347(4), 1993, pp. 353-362

Abstract

The effects of the selective 5-HT1A receptor agonist (R)-8-hydroxy-2(di-n-propylamino)tetralin [(R)-8-OH-DPAT] and the novel 5-HT1A antagonist (S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin [(S)-UH-3011 were studied with regard to the firing pattern of single mesencephalic dopamine (DA) neurons with extracellular recording techniques in chloralhydrate anesthetized male rats. Neuronal activity was studied with respect to firing rate, burst firing and regularity of firing. In the ventral tegmental area (VTA) low doses of (R)-8-OH-DPAT (2 - 32 mug/kg iv.) caused an increase in all three parameters. The effect on firing rate of DA neurons was more pronounced in the parabrachial pigmentosus nucleus than in the paranigral nucleus, the two major subdivisions of VTA. In the substantia nigra zona compacta (SN-ZC), (R)-8-OH-DPAT (2-256 mug/kg iv.) had no effect on firing rate and regularity of firing and only slightly increased burst firing. High doses of (R)-8-OH-DPAT (512 - 1024 mug/kg i.v.) decreased the activity of DA cells in both areas, an effect that was prevented by pretreatment with the selective DAD2 receptor antagonist raclopride. (S)-UH-301 (100-800 mug/kg iv.) decreased both firing rate and burst firing without affecting regularityof DA neurons in the VTA. In the SN-ZC, (S)-UH-301 decreased the firing rate but failed to affect burst firing and regularity of firing. These effects of (S)-UH-301 were blocked by raclopride pretreatment. Local application by pneumatic ejection of 8-OH-DPAT excited the DA cellsin both the VTA and the SN-ZC, whereas (S)-UH-301 inhibited these cells when given locally. These results show that 5-HT1A receptor relatedcompounds differentially affect the electrophysiological activity of central DA neurons. The DA receptor agonistic properties of these compound appear to contribute to the inhibitory effects of high doses of (R)-8-OH-DPAT and (S)-UH-301 on DA neuronal activity. Given the potential use of 5-HT1A receptor selective compounds in the treatment of anxiety and depression their effects on central DA systems involved in mood regulation and reward related processes are of considerable importance.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/09/20 alle ore 10:56:46