Non-serotonergic depression of spinal monosynaptic reflex transmission by 5-hydroxytryptophan

Administration of a 50 mg/kg (i.v.) dose of either 1-, or the racemic D,L-mixture of 5-hydroxytryptophan (5-HTP) in acute unanesthetized spinal (C-1) cats produced a depression of the lumbar monosynaptic response (MSR) amplitude when the reflex was evoked by supramaximal triceps surae (TS) nerve stimulation. Neither pretreatment with the serotonin receptor antagonists cincanserin or cyproheptadine, nor the L-aromatic amino acid decarboxylase inhibitor methyldopa antagonized the depressant effect of 5-HTP on the MSR in TS-stimulated animals. Administration of amitriptyline, a selective serotonin reuptake inhibitor, reversed the depression in the MSR amplitude produced by 5-HTP and produced an increase in the MSR above the original pre-5-HTP control level. These data suggest that 5-HTP has a depressant action upon spinal monosynaptic reflex transmission that is unrelated to an increase in spinal serotonergic activity. The site of the depressant effect of 5-HTP within the MSR pathway is postulated to be the la afferent terminal. This non-serotonergic 5-HTP action should be considered when interpreting the results of neuropharmacologic studies employing 5-HTP as a serotonin precursor.