Nonassociative explanations of behavioral changes induced by central cholinergic drugs

Studies concerning the effects of cholinergic stimulants and blockers on habituation, alternation, classical and instrumental conditioning, differentiation, and discrimination are summarized and discussed. This analysis suggests that many results originally ascribed to associative changes can be more economically accounted for by nonassociative factors inherent in the experiments. Furthermore, the data show that neither one of the more economical nonassuciative explanations at either the sensory, the drive, or the response level can by itself account for the complex interactions observed. The studies dealing with drug effects in lesioned animals, and those using intracerebral treatments, point out several sites of action of muscarinic agonists and antagonists in the septum, the hippocampus, the amygdala, the striatum, the hypothalamus, midline thalamic nuclei, and the reticular formation. Therefore, the provisional conclusion must be that central muscarinic systems subserve several functions, ranging from the modulation of consummatory responses to the control of motor-act differentiation. Both the drug and the lesion studies show not only that the fronto-limbic system has a considerable role in the latter process, but also that the localization of motor-act differentiation under a given drive depends both on the category of the cue, and on the category of the response. Some comparisons between the effects of muscarinic agonists and blockers and those of other drugs indicate that the alteration of sensory-motor relations caused by the former can be separated from (i) the motor hyperactivity caused by amphetamine, which is relatively less dependent on sensory factors; (ii) the selective (response enhancements caused by the indole hallucinogen LSD25, which appear to be amenable to a disinhibition of drive; (iii) the attenuation of punishment suppression by sedative and antianxiety agents (benzodiazepines and subhypnotic doses of barbiturates); and (iv) the hyperarousal or hyperreactivity syndrome induced by compounds which deplete central 5-hydroixytryphamine stores, such as panachlorophenylalanine.