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.