Norepinephrine and neural plasticity: the effects of xylamine on experience-induced changes in brain weight, memory, and behavior.

The hypothesis that norepinephrine (NE) is critically involved in neural plasticity was tested by administering xylamine, (N-2-chloroethyl-2-methylbenzylamine, 50 mg/kg ip) a noradrenergic neurotoxin, to young rats prior to maze training or environmentally enriched housing. In saline-treated rats, exposure to enriched conditions significantly increased the weight of occipital, dorsal, and ventral cortices and the remaining brain compared to individually housed rats. In xylamine-treated rats, only the weight of dorsal cortex increased with exposure to enriched conditions. Maze training increased the weight of dorsal and ventral cortices of saline-treated animals compared to rats without training. However, maze training did not increase brain weights of xylamine-treated rats compared to those of xylamine-treated controls. Xylamine treatment did not reduce brain weights of individually housed animals. Behavior was assessed with spatial learning on a holeboard maze and with investigatory measures of locomotion and hole investigation in a multicompartmented arena. Spatial working memory on the holeboard maze was not impaired by xylamine treatment. Arena measures were affected mainly by the housing condition, testing condition, and strain of rat (Long-Evans vs Wistar), with only subtle changes in behavior induced by NE depletion. Thus, an intact NE projection was required for environmentally dependent changes in cortical morphology. In contrast, measures of memory and investigatory behavior were not dependent on an intact noradrenergic projection. These results support the hypothesis that NE facilitates selective neuronal changes, and that the impairment in cortical weight gain does not results from a general impairment of growth or a secondary response to reduced exploration and activity.