Serotonin-lesion myoclonic syndromes. I. Neurochemical profile and S-1 receptor binding.
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 neocortex, 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, CaCl2, and pargyline. Without ascorbate, binding was specific, saturable, region-dependent, and non-linear with high (Kd 1-3 nM) and low affinity (10-20 nM) components but no cooperativity (0.8 less than nH less than 1.0). Bmax and Kd 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 Bmax induced by ascorbic acid (1 mM). The effects of assay conditions exceeded the changes sometimes reported in S-1 receptor Bmax after 5-HT lesions.
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology*; D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001679:Biogenic Amines / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D004102:Dihydroxytryptamines / Q000494:pharmacology*; D004347:Drug Interactions; D005277:Fenfluramine / Q000494:pharmacology*; D008297:Male; D009207:Myoclonus / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D013577:Syndrome; D010133:p-Chloroamphetamine / Q000494:pharmacology*
D000662:Amphetamines; D001679:Biogenic Amines; D004102:Dihydroxytryptamines; D011985:Receptors, Serotonin; D005277:Fenfluramine; D015116:5,7-Dihydroxytryptamine; D010133:p-Chloroamphetamine; D006916:5-Hydroxytryptophan