Unlike systemic administration of p-chloroamphetamine, direct intracerebral injection does not produce degeneration of 5-HT axons.
Systemic administration of the amphetamine derivative p-chloroamphetamine (PCA) causes degeneration of 5-HT axon terminals in rat brain. The present study was designed to determine whether PCA induces neurotoxic effects by a direct action on 5-HT axon terminals. PCA was administered by microinjection directly into the cerebral cortex of rats. Continuous intracerebral infusions were made over extended time periods (10 min-48 h) to explore whether the induction of neurotoxicity requires a prolonged exposure of axon terminals to the drug. Two weeks after drug administration, brain sections that passed through the injection site were processed for 5-HT immunohistochemistry. The 5-HT innervation of cerebral cortex in PCA-injected animals was compared with that after intracortical injection of saline or of 5,7-dihydroxytryptamine. The results demonstrate that, in the concentrations used, direct application of PCA into the neocortex does not elicit axonal degeneration, even after a continuous infusion for 2 days. This finding suggests that PCA itself is not directly toxic to 5-HT axons.
Berger
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UV
Johns Hopkins University, School of Medicine, Department of Neuroscience, Baltimore, Maryland 21205.
Molliver
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ME
Grzanna
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R
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D007150:Immunohistochemistry; D007267:Injections; D008297:Male; D009410:Nerve Degeneration; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012965:Sodium Chloride / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000008:administration & dosage* / Q000494:pharmacology
D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D012965:Sodium Chloride; D010133:p-Chloroamphetamine