REGION-DEPENDENT AND NEUROTRANSMITTER-DEPENDENT SPECIES AND STRAIN DIFFERENCES IN DSP-4-INDUCED MONOAMINE DEPLETION IN RODENTS

The neuro toxin N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is commonly used as a chemical tool to induce selective denervation of noradrenergic terminals arising from the locus coeruleus and to study the molecular mechanisms underlying degeneration of central noradrene rgic axons in rodents. Monoamine depletion in different rodent species after DSP-4 is generally assumed to occur with a similar pattern. To verify this assumption, in the present study we evaluated the differen t patterns of monoamine depletion produced by DSP-4 in different brain regions of two different strains of mice and rats 3, 7 and 14 days af ter DSP-4 administration. In this report, we show that there are evide nt species and strain differences concerning the pattern of norepineph rine depletion in various brain regions. Moreover, serotonin levels ar e fully preserved following DSP-4 in mice, whereas there is a signific ant serotonin decrease in specific brain regions after the same dose o f DSP-4 in rats. Apart from disclosing species and strain variability among rodents in neurotoxin-induced monoamine depletion, these finding s suggest that DSP-4 should be considered as a different neurotoxin, d epending on the species and strain in which it is administered. (C) 19 96 Academic Press Limited