Several experiments indicated that a cholinergic system in the brain antagonizes a 2nd system, which activates behavior. Neuropharmacological considerations suggested certain drugs with which the activity of these systems could be altered. These experiments indicated that the cholinergic system acts selectively by preferentially antagonizing the effects of activation on unrewarded behavior. That is, there appears to be a cholinergic involvement in the mediation of the effects of nonreward. Although such interpretations are necessarily very tentative, there are inferential grounds for supposing that a cholinergic system selectively antagonizes the effect of activation on certain behavior and that the basis of this selectivity is the extent to which that behavior is unrewarded.

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Two groups of rats, one with electrolytic lesions of the medial septum and one group of operated controls, were observed over an extended period of time and tested ia a variety of behavioral situations. The lesioned subjects were observed to be hyperplacid and showed increased sperm-plugging postoperatively. These animals also demonstrated a marked deficit in spontaneous alternation and a depression in running-wheel activity. The results of a simple approach-learning task demonstrated enhanced acquisition and increased resistance to extinction for the experimental animals. These findings were related to the septal mediation of hippocampal and extrahippocampal functions.