title: Depletion of serotonin using p-chlorophenylalanine (PCPA) and reserpine protects against the neurotoxic effects of p-chloroamphetamine (PCA) in the brain.
abstract: The present study attempts to determine whether the neurotoxicity of p-chloroamphetamine (PCA) is dependent on a releasable pool of serotonin (5-HT). Rats treated with PCA alone or with reserpine and PCA exhibit a profound loss of 5-HT innervation in cerebral cortex after a 2-week survival period. However, depletion of 5-HT by combined treatment with p-chlorophenylalanine (PCPA) and reserpine provides substantial protection against the neurotoxic effects of PCA. These results indicate that release of 5-HT is a necessary step in the neurotoxicity of PCA and that a peripheral source of 5-HT is involved. We suggest that 5-HT release from platelets into the peripheral circulation may result in the formation of a neurotoxic 5-HT metabolite.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: U V
authors.initials: UV
authors.lastname: Berger
authors.forename: R
authors.initials: R
authors.lastname: Grzanna
authors.forename: M E
authors.initials: ME
authors.lastname: Molliver
mesh_terms: D000662:Amphetamines / Q000633:toxicity*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010134:Fenclonine / Q000494:pharmacology*; D008297:Male; D009498:Neurotoxins; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012110:Reserpine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000633:toxicity*
chemical_list: D000662:Amphetamines; D009498:Neurotoxins; D012701:Serotonin; D010133:p-Chloroamphetamine; D012110:Reserpine; D010134:Fenclonine