Effects of cerebral depletion of norepinephrine on conditioned avoidance responding in Sprague-Dawley and Fischer rats.

Abstract

Block of conditioned avoidance responding (CAR) in the rat is a property of all antipsychotic agents. To determine whether cerebral norepinephrine (NE) is crucial for CAR, the effect of depletion of cerebral NE was examined both during acquisition and retention of a CAR task in Sprague-Dawley and Fischer 344 male rats. In examining acquisition of CAR, DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] (50 mg/kg, IP) was given to naive rats from each strain. In one control group, desmethylimipramine (DMI, 20 mg/kg, IP -30 min), which inhibits the uptake of DSP-4 and its subsequent neurotoxic effect, was given prior to DSP-4. After DSP-4, all animals were tested for acquisition of CAR in a discrete trial paradigm in striatum, and brain stem were removed for NE and dopamine assay using HPLC. In examining retention of CAR, the effect of DSP-4 on the CAR of trained rats were observed. DSP-4 produced an almost total depletion of cortical NE and about 50% reduction of NE in the brain stem in both strains and in both tests. In the first experiment, DSP-4 failed to significantly diminish CAR acquisition in either strain, although there was a trend towards a DSP-4-induced deficit. Interestingly, DSP-4 caused no decrement in CAR in trained rats of either strain, but did significantly impair further acquisition of CAR in Sprague-Dawley rats. The data demonstrate cerebral NE is not critical for retention of CAR, but suggest a possible role for NE in the acquisition of CAR.