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Korean Journal of Psychopharmacology ; : 71-79, 1999.
Article Dans Coréen | WPRIM | ID: wpr-201658

Résumé

OBJECTIVES: The present study assessed the effect of trazodone on the cerebral hemodynamics of male Sprague-Dawley rats. METHOD: The changes of regional cerebral blood flow(rCBF) and pill arterial diameter were measured by laser-Doppler flowmetry and by a videomicroscopy, respectively. The changes in vascular tone and intracellular free Ca2+ concentration ([Ca2+]i) of isolated basilar artery were simultaneously measured using a small vessel myograph and a cation measurement system, respectively. RESULT: Both the rCBF and the pill arterial diameter were dose-dependently decreased by systemic administration of trazodone(0.3-10 mg/kg, i.v.), but not by topical application of trazodone(10-300 micrometer). Pretreatment with 5-HT(2A/2C) receptor antagonist(ketanserin or ritanserin, 1 mg/kg, i.v., respectively) significantly blocked the changes in rCBF induced by trazodone. m-Chlorophenylpiperazine(mCPP ; 0.1-3 mg/kg, i.v. or 5-500 micrometer topical), a major active metabolite of trazodone, also dose-dependently decreased the rCBF as well as the pial arterial diameter. The mCPP-induced decreases in rCBF were significantly blocked by ketanserin. Pretreatment with itraconazole(1 mg/kg, p.o.), a selective inhibitor of CYP3A4, a subfamily of cytochrome P450, markedly attenuated the trazodone-induced changes in rCBF. In an isolated rat basilar arterial strip loaded with fura-2/AM, mCPP(5-500 micrometer caused a vasoconstriction in association with increases in [Ca2+]i, in a concentration-dependent manner. Pretreatment with 1 micrometerketanserin strongly blocked the effects of mCPP on the vascular tone as well as on the [Ca2+]i, of rat basilar artery. CONCLUSION: These results suggest that trazodone decreases rCBF through stimulation of 5-HT(2A/2C) receptors by its active metabolite, mCPP.


Sujets)
Animaux , Humains , Mâle , Rats , Artère basilaire , Cytochrome P-450 enzyme system , Hémodynamique , Kétansérine , Fluxmétrie laser Doppler , Vidéomicroscopie , Rat Sprague-Dawley , Ritansérine , Trazodone , Vasoconstriction
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