Repeated administration of amphetamine (AM) or other stimulants (e.g., cocaine) to either humans or animals results in a gradual augmentation of behavior (sensitization) which, in many respects resembles paranoid schizophrenia. This """"""""model psychosis"""""""" is thought to be importantly dependent of brain dopamine (DA). The major thesis of the present proposal is that many effects of stimulants of potential relevance to psychosis may be the result of these agents mimicking the effects of stress on DA function. Specifically, we propose that: 1) Repeated stress can sensitize the behavioral response of the organism to the effects of acute stimulant administration or vice-versa and, 2) Repeated stress can sensitize an organism to subsequent stress just as chronic AM treatment can enhance the behavioral influence of subsequent AM administration. A variety of stimulants and stressors will be employed to test this model which will be examined both from a behavioral and biochemical standpoint.
Showing the most recent 10 out of 17 publications