Differential effects of selective dopamine, norepinephrine or catecholamine depletion on activity and learning in the developing rat

Abstract

The present experiment investigated the behavioral changes which occurred following neonatal depletion of central catecholamine systems in the rat. The behavioral effects which resulted from selective dopamine (DA) depletion were compared with those resulting from selective norepinephrine (NE) depletion as well as depletion of both catecholamines (CA). Neonatal 6-hydroxydopamine (6-OHDA) was administered intracisternally at 5 days of age following pretreatment with desmethylimipramine in order to selectively deplete DA. NE levels were reduced by intraperitoneal injections of 6-OHDA at 1 and 2 days of age. Depletion of both catecholamines was effected by combining the procedures used for selective depletion of both DA and NE. Activity was time sampled during an hour at 3 preweanling ages. Avoidance and escape learning were measured in a T maze when pups were 20 days of age and in a Shuttlebox apparatus on day 28. Results revealed that DA and CA depleted animals were hyperactive in comparison to controls and displayed severe learning impairments in both T maze and Shuttlebox performance. In contrast, NE depleted animals showed activity levels which were similar to controls but were significantly impaired on both learning paradigms. These results suggest that selective lesions of DA and NE in infancy lead to a constellation of behaviors which are distinctly unique. The implications of these findings is discussed in terms of clinical research into the Attentional Deficit Disorder of childhood.