Partial denervation of the locus coeruleus projections by treatment with the selective neurotoxin DSP-4 potentiates the long-term effect of parachloroamphetamine on 5-hydroxytryptamine metabolism in the rat

Abstract

Pretreatment with N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP-4), a neurotoxin highly selective for the locus coeruleus (LC) projections, has recently been found to increase the vulnerability of dopaminergic nerve terminals to their selective neurotoxins. In the present study, combined treatment with a selective serotonergic (5-HT-ergic) neurotoxin parachloroamphetamine (PCA) at low doses (1 or 2 mg/kg) and a low dose of DSP-4 (10 mg/kg) led to larger decreases in 5-hydroxyindoleacetic acid (5-HIAA) levels in several brain regions than with either toxin alone. A reduction in 5-hydroxytryptamine (5-HT) turnover was observed only after the combined treatment with low doses of DSP-4 and PCA. When DSP-4 (10 mg/kg) was administered 2 months before PCA (2 mg/kg), the effect of PCA on cortical 5-HT levels was augmented, as was the effect on cortical and hypothalamic 5-HIAA levels. Conclusively, after limited alterations in the LC projections, there is an enhanced sensitivity of 5-HT-ergic nerve terminals to PCA.