The effect of repeated treatment with oxaprotiline enantiomers on central 5-HT receptor subpopulations
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The effect of repeated administration of/+/-OXA /a noradrenaline /NA/ uptake inhibitor/ and /-/-OXA /devoid of an effect on the NA uptake but a clinically active antodepressant drug/ on central 5-HT receptor subpopulations was studied./-/-OXA given repeatedly, but not acutely, attenuated the 8-OH-DPAT -induced hypothermia in mice./+/-OXA administered acutely, as well as repeatedly, was inactive in that test. The 8-OH-DPAT -induced syndrome in rats was attenuated by both OXA isomers administered either acutely or repeatedly. The hypothermia induced by m-CPP in mice was attenuated by single-dose administration of /+/-OXA and /-/-OXA; when given repeatedly, /+/-OXA increased the action of m-CPP. /-/-OXA administered repeatedly was inactive in that test. Either single or repeated administration of /+/-OXA had practically no effect on the depression of exploratory activity induced by m-CPP./-/-OXA administered acutley or repeatedly attenuated the effect of m-CPP in the same manner, Acute, but not chronic, administration of /-/-OXA reduced the number of head-twitch episodes induced by 5-HTP in mice. Repeated, but not acute, treatment with /+/-OXA attenuated the effect of 5-HTP. The obtained results indicate that /+/-OXA administered repeatedly increases the reactivity of 5-HT1B receptors, decreases the reactivity of 5-HT2 receptors, and has no effect on the reactivity of 5-HT1A-(pre- and postsynaptic) and 5-HT1C-receptors. /-/-OXA given repeatedly decreases the reactivity of presynaptic 5-HT1A receptors and has no influence on the reactivity of postsynaptic 5-HT1A-, 5-HT1B-, 5-HT1C- and 5-HT2 -receptors.
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