The ultimate goal of this proposed research is to understand the role of brain neurotransmitter systems in the actions of psychotropic drugs and in the maintenance of behavior. The research will focus on the behavioral involvement of dopamine, norepinephrine, and 5-hydroxytryptamine. Behavior will be measured using a computer-controlled real-time data application system. The research will employ two closely related parallel approaches. In the first approach, a sensitive and specific operant behavioral screen that detects drugs with antidepressant action will be used to determine the catecholaminergic and serotonergic components of antidepressant drugs effects. Also, studies will be done to determine whether norepinephrine, dopamine and 5-hydroxytryptamine systems interact to produce antidepressant effects. The goal of this research is to elucidate the neurochemical changes that mediate antidepressant drug effects on operant behavior. Knowledge of these neurochemical changes could provide insight into the pathophysiology of depression. For the second approach, studies will be done to determine the neurochemical mechanisms that mediate interactions between drugs, behavior and the environment. Drug effects on behavior depend not only on the specific drug and dose of the drug, but also depend on the environment in which the drug is administered and on the ongoing behavior. Therefore, neurochemical change will be measured as a function of systematically varied environmental and behavioral parameters. Knowledge of environmental and behavioral parameters as independent variables that alter brain chemistry would provide additional insight into the pathophysiology of mental illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH011191-24
Application #
3565431
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1977-12-15
Project End
1993-11-30
Budget Start
1989-02-01
Budget End
1989-11-30
Support Year
24
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Bergmann, B M; Seiden, L S; Landis, C A et al. (1994) Sleep deprivation in the rat: XVIII. Regional brain levels of monoamines and their metabolites. Sleep 17:583-9
Richards, J B; Sabol, K E; Hand, T H et al. (1994) Buspirone, gepirone, ipsapirone, and zalospirone have distinct effects on the differential-reinforcement-of-low-rate 72-s schedule when compared with 5-HTP and diazepam. Psychopharmacology (Berl) 114:39-46
Marek, G J; Heffner, T G; Richards, J B et al. (1993) Effects of caffeine and PD 116,600 on the differential-reinforcement-of-low rate 72-S (DRL 72-S) schedule of reinforcement. Pharmacol Biochem Behav 45:987-90
Richards, J B; Sabol, K E; Seiden, L S (1993) Fluoxetine prevents the disruptive effects of fenfluramine on differential-reinforcement-of-low-rate 72-second schedule performance. J Pharmacol Exp Ther 267:1256-63
Richards, J B; Sabol, K E; Seiden, L S (1993) DRL interresponse-time distributions: quantification by peak deviation analysis. J Exp Anal Behav 60:361-85
Richards, J B; Seiden, L S (1991) A quantitative interresponse-time analysis of DRL performance differentiates similar effects of the antidepressant desipramine and the novel anxiolytic gepirone. J Exp Anal Behav 56:173-92
Hand, T H; Marek, G J; Seiden, L S (1991) Comparison of the effects of mianserin and its enantiomers and metabolites on a behavioral screen for antidepressant activity. Psychopharmacology (Berl) 105:453-8
Li, A A; Marek, G J; Hand, T H et al. (1990) Antidepressant-like effects of trazodone on a behavioral screen are mediated by trazodone, not the metabolite m-chlorophenylpiperazine. Eur J Pharmacol 177:137-44
Marek, G J; Vosmer, G; Seiden, L S (1990) Pargyline increases 6-hydroxydopamine levels in the neostriatum of methamphetamine-treated rats. Pharmacol Biochem Behav 36:187-90
Li, A A; Marek, G J; Vosmer, G et al. (1989) Long-term central 5-HT depletions resulting from repeated administration of MDMA enhances the effects of single administration of MDMA on schedule-controlled behavior of rats. Pharmacol Biochem Behav 33:641-8

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