Abstract

Concepts and experimental results taken frombehavioral pharmacology, functional brain imaging,brain physiology, and behavioral neuroscience, wereused to develop the hypothesis that behavioraltolerance can, in part, be attributed to cellulartolerance. It is argued that task specific activationof circumscribed neuronal populations gives rise tocorresponding increases in regional cerebral bloodflow such that neurons related to task performance areexposed to higher effective doses of blood-borne drugthan neuronal groups not highly activated by thebehavioral task. Through this cerebral hemodynamicregulatory mechanism cellular tolerance phenomena canat least partially account for behavioral tolerance(i.e., tolerance conferred through drugged practice).