Differential effects of ( R)- and ( S)-8-hydroxy-2-(di- n-propylamino)tetralin on the monosynaptic spinal reflex in rats

Abstract

We examined the effects of ( R)- and ( S)-8-hydroxy-2-(di- n-propylamino)tetralin hydrobromide (8-OH-DPAT) on the monosynaptic spinal reflex in rats. In intact rats, ( R)-8-OH-DPAT (10 μg/kg, i.v.) enhanced the amplitude of the monosynaptic reflex, whereas at 100 μg/kg, it reduced the amplitude. ( S)-8-OH-DPAT enhanced the monosynaptic reflex dose-dependently. In spinalized rats, ( R)-8-OH-DPAT produced dose-dependent inhibition, but the ( S)-enantiomer did not affect the monosynaptic reflex. Pretreatment with spiroxatrine or 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190) inhibited ( R)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did 5-hydroxytryptamine (5-HT) depletion. Ketanserin reduced the effect of ( R)-8-OH-DPAT. These pretreatment regimens had no effect on the monosynaptic reflex depression produced by the ( R)-enantiomer in intact and spinalized rats. Pretreatment with prazosin inhibited ( S)-8-OH-DPAT-induced monosynaptic reflex enhancement in intact rats, as did noradrenaline and 5-HT depletion. These results suggest that supraspinal 5-HT 1A receptors and the descending serotonergic system are involved in the stimulatory effect of ( R)-8-OH-DPAT on the monosynaptic reflex, while both the descending serotonergic and noradrenergic systems, the latter acting via α 1-adrenoceptors, are involved in the effect of the ( S)-enantiomer on this reflex.