Near-total loss of 'learning' and 'memory' as a result of combined cholinergic and serotonergic blockade in the rat.

Previous work has indicated that activation of the cerebral cortex (i.e. elicitation of low-voltage fast activity in the neocortex and rhythmical slow activity in the hippocampus) is dependent on corticipetal cholinergic and serotonergic projections. Treatment with a combination of p-chlorophenylalanine (an inhibitor of the synthesis of serotonin) plus atropine or scopolamine (muscarinic cholinergic antagonists) can suppress all cerebral activation. In this paper, the behavioral effects of single or combined blockade of cholinergic and serotonergic neurotransmission were studied using a shock avoidance test, an open field test, a swim-to-platform test, a hypothalamic self-stimulation test and a test of grooming behavior. The results show that blockade of cerebral activation produces a condition analogous to global dementia but does not produce sleep or coma. The hypothesis that cholinergic and serotonergic neurotransmission provides a basis for learning and memory is discussed critically.