Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH024114-12
Application #
3374869
Study Section
(SRCM)
Project Start
1988-01-01
Project End
1990-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

McAllister-Sistilli, C G; Caggiula, A R; Knopf, S et al. (1998) The effects of nicotine on the immune system. Psychoneuroendocrinology 23:175-87
Caggiula, A R; Antelman, S M; Palmer, A M et al. (1996) The effects of ethanol on striatal dopamine and frontal cortical D-[3H]aspartate efflux oscillate with repeated treatment. Relevance to individual differences in drug responsiveness. Neuropsychopharmacology 15:125-32
Antelman, S M; Caggiula, A R; Kiss, S et al. (1995) Neurochemical and physiological effects of cocaine oscillate with sequential drug treatment: possibly a major factor in drug variability. Neuropsychopharmacology 12:297-306
Caggiula, A R; Epstein, L H; Antelman, S M et al. (1993) Acute stress or corticosterone administration reduces responsiveness to nicotine: implications for a mechanism of conditioned tolerance. Psychopharmacology (Berl) 111:499-507
Yehuda, R; Antelman, S M (1993) Criteria for rationally evaluating animal models of posttraumatic stress disorder. Biol Psychiatry 33:479-86
Antelman, S M; Kocan, D; Knopf, S et al. (1992) One brief exposure to a psychological stressor induces long-lasting, time-dependent sensitization of both the cataleptic and neurochemical responses to haloperidol. Life Sci 51:261-6
Antelman, S M; Caggiula, A R; Knopf, S et al. (1992) Amphetamine or haloperidol 2 weeks earlier antagonized the plasma corticosterone response to amphetamine;evidence for the stressful/foreign nature of drugs. Psychopharmacology (Berl) 107:331-6
Caggiula, A R; Epstein, L H; Antelman, S M et al. (1991) Conditioned tolerance to the anorectic and corticosterone-elevating effects of nicotine. Pharmacol Biochem Behav 40:53-9
Antelman, S M; Caggiula, A R; Kocan, D et al. (1991) One experience with 'lower' or 'higher' intensity stressors, respectively enhances or diminishes responsiveness to haloperidol weeks later: implications for understanding drug variability. Brain Res 566:276-83
Antelman, S M; Cunnick, J E; Lysle, D T et al. (1990) Immobilization 12 days (but not one hour) earlier enhanced 2-deoxy-D-glucose-induced immunosuppression: evidence for stressor-induced time-dependent sensitization of the immune system. Prog Neuropsychopharmacol Biol Psychiatry 14:579-90

Showing the most recent 10 out of 17 publications