An investigation of the role of cortical and cerebellar noradrenaline in associative motor learning in the rat

Abstract

The role of the noradrenergic projections from the locus coeruleus to the cerebral and cerebellar cortices in the learning of a novel motor response was investigated using two techniques of administration of the relatively selective neurotoxin, 6-hydroxydopamine (6-OHDA). In one technique, 8 μg of 6-OHDA was stereotaxically injected bilaterally into the fibres of the dorsal noradrenergic bundle in the mesencephalon. This produced severe depletion of cortical and hippocampal noradrenaline (NA) but did not damage the cerebellar projection. The second 6-OHDA technique involved intraperitoneal injection of 100 mg/kg of 6-OHDA into neonatal rats on days 1, 3, 5, 7, 9, and 11 after birth. This produced depletions of cortical and hippocampal NA comparable to the dorsal bundle technique, but also gave a profound loss of cerebellar NA. Neither technique altered striatal dopamine (DA). These animals were tested on the acuisition of a complex motor learning task involving the pulling or pushing of a ball out of a tunnel in order to reach food. Neither preparation was impaired on acquisition of this novel motor response, nor in tests of behavioural flexibility requiring the transfer from pull to the push response and vice versa. Both NA depleted preparations, however, showed a marked difference from normals when tested in extinction. When food was no longer presented, the 6-OHDA treated animals continued emitting the response for longer and with greater rapidity than control animals. This resistance to extinction is a further demonstration of the role of the dorsal noradrenergic bundle in mechanisms involved in the extinction process. The findings are discussed in relation to noradrenergic theories of associative and motor learning and to previously demonstrated alterations in the extinction process in 6-OHDA treated animals.