DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion.

N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) (50 mg/kg IP), a new selective noradrenaline (NA) neurotoxin, was found to cause a severe impairment of the acquisition of a two-way active avoidance task 1 week following administration, an effect that was blocked by the selective NA uptake inhibitor desipramine. In a second experiment, systemically injected 6-OHDA (2 x 30 mg/kg IP) was not found to cause any avoidance impairment, although its effects upon peripheral NA were still evident 21 days after administration: The peripheral NA depletion caused by DSP4 almost disappeared 14 days after injection. In a third experiment, the avoidance impairment induced by DSP4 was produced even 10 weeks after treatment. Data from both the shuttlebox experiment and an activity box experiment suggest that the acquisition impairment is not readily explained on the basis of some deficit in spontaneous behavior or an altered perception of pain. The present data suggest that the effect of DSP4 upon active avoidance acquisition is mediated via central, and not peripheral NA neurons.