NEURONAL MECHANISMS MEDIATING DRUG-INDUCED COGNITION ENHANCEMENT - COGNITIVE ACTIVITY AS A NECESSARY INTERVENING VARIABLE

The conceptual foundations of a research aimed at the determination of potential neuronal, neuropharmacological, and behavioral/cognitive me chanisms mediating drug-induced cognition enhancement are discussed. T he available evidence justifies a focus on attentional processes as a target for drug-induced cognition enhancement. Neuropharmacological me chanisms that may mediate drug-induced enhancement of attentional func tions are proposed to interact necessarily with attention-associated n euronal activity. The elements of a transsynaptic approach to increase the excitability of basal forebrain cholinergic neurons and hence, at tentional functions are discussed. Experimental tests of this hypothes is require the demonstration of interactions between cognition-induced increases in the activity of cortical cholinergic afferents and the e ffects of putative cognition enhancers. The available data illustrate that the effects of benzodiazepine receptor (BZR) agonists and inverse agonists on cortical acetylcholine (ACh) efflux interact with the sta te of activity in this system. The feasibility, potential heuristic po wer, and the experimental and conceptual problems of studies attemptin g to simultaneously assess drug effects on behavioral/cognitive abilit ies, ACh efflux, and neuronal activity have been revealed by an experi ment intended to correlate performance in a task measuring sustained a ttention with medial prefrontal ACh efflux and medial prefrontal singl e-unit activity. The rational development of a psychopharmacology of c ognition enhancers requires a union among behavioral/cognitive pharmac ology, neuropharmacological and electrophysiological approaches.