PARADOXICAL BLOCKADE BY p-CHLOROPHENYLALANINE OF 5-HYDROXYTRYPTOPHAN FACILITATORY ACTIONS ON SPINAL REFLEXES

¹ Department of Pharmacology, University of Illinois at the Medical Center, Chicago, Illinois

Cats pretreated with p-chlorophenylalanine (pCPA), given as two injections of 300 mg/kg 24 hours apart, were spinalized and prepared for reflex recording 48 to 96 hours after the initial dose. Unexpectedly, pCPA pretreatment completely prevented the usual facilitatory effects of 5-hydroxytryptophan (5-HTP) on the monosynaptic reflex. Reserpine pretreatment (0.5 mg/kg) greatly enhanced the facilitatory effect of 5-HTP on the monosynaptic reflex. pCPA markedly reduced cord 5-hydroxytryptamine (5-HT) without significantly affecting cord norepinephrine levels, whereas reserpine reduced the levels of both amines. Cats pretreated with either pCPA or reserpine accumulated large quantities of 5-HT after administration of 5-HTP. pCPA pretreatment did not block the facilitatory effects of 5-HTP in chronic spinal cats nor in cats also pretreated with reserpine. It is suggested that blockade of the facilitatory effects of 5-HTP by pCPA results from increased retention of newly synthesized 5-HT by the nearly empty synaptic storage vesicles. This prevents significant overflow of 5-HT onto subsynaptic receptors. Conversely, the potentiating action of reserpine results from blockade of the entry of newly formed 5-HT into synaptic vesicles, thus increasing the synaptic overflow of 5-HT.