Effects of amphetamine and medial septal lesions on acquisition and retention of radial maze learning in rats

Procholinergic drugs have failed to overcome the memory deficit induced by alterations of the cholinergic system because their neurochemical target in the brain is either lacking or disorganised. However, there are many reports on a relative involvement of the dopaminergic system in learning and memory that may compensate for the cholinergic deficit because of the interaction or balance between neurotransmitters and the redundancy of the brain. The aim of our experiments is to examine the activation of the dopaminergic system on the performance of normal and medial septal lesioned rats in the radial maze test involving continuous choices. In the first experiment different groups of normal rats were treated with either 0.5, 1.0 or 2.0 mg/kg of D-amphetamine and tested in the radial maze. In the second experiment, medial septal lesioned rats which had learnt pre-op the radial maze test were retested a month later. Amphetamine had no effect on the memory measures provided by the radial maze test in normal and lesioned rats, but non-memory measures were significantly affected: amphetamine decreased the sequential choice responses and the time taken by the rats to perform the test. The present results show that the activation of the dopaminergic system does not compensate for the alteration of the cholinergic activity inducing amnesia, however, they support the recent data on the improving effect of amphetamine on locomotor activity. The interpretation of drug/lesion interaction effects is discussed in this paper in relation to the literature on the effect of promnesic drugs