DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), a new noradrenaline neurotoxin, and stimulus conditions affecting acquisition of two-way active avoidance.

Several stimulus (conditioned stimulus [CS] and unconditioned stimulus) variables known to affect the rate of acquisition of the two-way active avoidance task were investigated in rats treated with the novel selective noradrenaline neurotoxin DSP4 (50 mg/kg, ip). Although the DSP4 rats did not demonstrate the linear relation between CS duration and avoidance acquisition to the same extent as the control rats, their avoidance performance was as drastically disrupted as that of the controls both by preexposure to the CS and by increasing levels of shock intensity. The DSP4 rats also evidenced fear retention for the shuttle box cues previously associated with inescapable shocks to as marked a degree as control rats. Biochemical data indicated profound noradrenaline depletion in the cortex and hippocampus and a lesser depletion in the hypothalamus. It seems unlikely that the small serotonin depletions evidenced here can account for the avoidance deficits. The present findings offer a behavioral characterization of the consistent DSP4-induced impairment of two-way active avoidance acquisition.