Region- and neurotransmitter-dependent species and strain differences in DSP-4-induced monoamine depletion in rodents

The neurotoxin N-(-2-chloroethyl)-N-ethyl-2-bromobenzyl (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 noradrenergic 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 different 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 after DSP-4 administration. In this report, we show that there are evident species and strain differences concerning the pattern of norepinephrine depletion in various brain regions. Moreover, serotonin levels are fully preserved following DSP-4 in mice, whereas there is a significant serotonin decrease in specific brain regions after the same dose of DSP-4 in rats. Apart from disclosing species and strain variability among rodents in neurotoxin-induced monoamine depletion, these findings suggest that DSP-4 should be considered as a different neurotoxin, depending on the species and strain in which it is administered.