Novelty-oriented behavior in the rat after selective damage of locus coeruleus projections by DSP-4, a new noradrenergic neurotoxin

Open-field behavior and reactions to a novel object (white-colored cube) or a familiar object (drinking bottle) were investigated in rats treated with DSP-4 N-(2-chloroethyl) -N-ethyl-2-bromobenzylamine, a new noradrenergic neurotoxin which selectively damages locus coeruleus projections. Altered behavior in the open-field and in the presence of the novel object (white cube) was observed in DSP-4 rats. This was reflected in decreased exploration-oriented locomotor responses and in longer latencies to approach the novel cube. Also, there was a trend towards fewer center entries and a shorter duration of object exploration. Although these behavioral responses of DSP-4 rats were indicative of enhanced neophobia, other measures of emotionality, such as grooming and defecation, were either unchanged or slightly decreased. Moreover, when the familiar drinking bottle was present in the open-field, water-deprived DSP-4 rats showed no change in any measure of fear including the latency to the first approach and lick, and the duration of the licking episodes. The results of this study suggest that noradrenergic neurons of the locus coeruleus are involved in the regulation of certain, but not all, novelty-oriented responses in the rat. Explorative behavior in the novel environment seems to be particularly dependent on central noradrenaline.