Serotonin-lesion Myoclonic syndromes. I. Neurochemical profile and S-1 receptor binding

Abstract

This paper and the following one describe the effects of l-5-hydroxytryptophan (5-HTP) (after 3 intracisternal injections of 5,7-dihydroxytryptamine (DHT), fenfluramine (FF),p-chloroamphetamine (PCA) and drug combinations on (i) brain regional amine concentration (HPLC with LEC) and serotonin S-1 receptor binding; and (ii) ‘serotonergic’ behaviors in the same adult rats. Serotonin (5-HT) neurotoxins produced significantly different regional profiles of 5-HT depletion. Multiple DHT injections caused a 90–100% depletion of 5-HT concurrently in neocorex, hippocampus, striatum, septum/accumbens, pons, cerebellum, and cervical cord. Only PCA significantly depleted midbrain. Drug combinations with DHT resembled DHT alone rather than additive depletions, except for PCA + DHT, which produced a hybrid pattern of depletion. The S-1 binding assay, using cold 5-HT to displace [ 3H]5-HT, was performed with and without ascorbate, EDTA, CaC1 2, and pargyline. Without ascorbate, binding was specific, saturable, region-dependent, and non-linear with high (K d 1–3nM) and low affinity (10–20 nM) components but no coopeerativity (0.8 <11.0). B max andK d did not differ significantly between vehicle- and drug-treated animals in neocortex, hippocampus, striatum, thalamus, hypothalamus, midbrain, pons, medulla, cervical cord, cerebellum, or septum/accumbens two weeks after lesioning, while the assay did detect a 60% reduction in B max induced by ascorbic acid (1 mM). The effects of assay conditions exceeded the changes sometimes reported in S-1 receptor B max after 5-HT lesions.