The objectives of this research are to utilize measurements related to dopaminergic neuronal transmission in order to elucidate the actions of neuroleptic and psychotogenic drugs and to assist in classification and treatment assessment in the non-organic psychotic disorder. These studies are directed toward an understanding of schizophrenia and related psychotic disorders. The following specific projects are proposed 2) an assessment of a neuroleptic (haloperidol) and a benzodiazepine (diazepam) alone and in combination upon regional brain dopamine (DA) metabolism in the rat 2) measurement of regional changes in brain DA metabolism produced by psychotogenic drugs and an exploration of pharmacological approaches for reversing these changes 3) use of plasma catecholamine metabolites as markers for a subgroup of patients with psychotic disorders who may have unique clinical characteristics. Methods to be employed include acute and chronic drug administration to rats and measurement of regional brain homovanillic acid (HVA), dopamine (DA), methoxyhydroxyphenothylglycol (MHPG), and norepinephrine (NE). Clinical studies will involve measurements of catecholamine metabolites in plasma in conjunction with a variety of clinical variables in psychotic inpatients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH028216-14
Application #
3375019
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1979-05-01
Project End
1991-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
14
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Mazure, C M; Quinlan, D M; Bowers Jr, M B (1997) Recent life stressors and biological markers in newly admitted psychotic patients. Biol Psychiatry 41:865-70
Davis, M; Hitchcock, J M; Bowers, M B et al. (1994) Stress-induced activation of prefrontal cortex dopamine turnover: blockade by lesions of the amygdala. Brain Res 664:207-10
Bowers Jr, M B; Mazure, C M; Greenfeld, D G (1994) Elevated plasma monoamine metabolites in eating disorders. Psychiatry Res 52:11-5
Bowers Jr, M B; Morton, J B (1994) Regional brain catecholamines and metabolites following THC, PCP and MK-801. Prog Neuropsychopharmacol Biol Psychiatry 18:961-4
Bowers Jr, M B (1993) Psychotic patients with increased plasma HVA and MHPG or increased HVA alone. Biol Psychiatry 34:584-6
Bowers Jr, M B; Mazure, C M; Nelson, J C et al. (1992) Lithium in combination with perphenazine: effect on plasma monoamine metabolites. Biol Psychiatry 32:1102-7
Mazure, C M; Nelson, J C; Jatlow, P I et al. (1992) Drug-responsive symptoms during early neuroleptic treatment. Psychiatry Res 41:147-54
Bowers Jr, M B; Morton, J B (1992) Diazepam antagonizes effects on dopamine metabolism produced by PCP receptor agonists. Prog Neuropsychopharmacol Biol Psychiatry 16:211-5
Bowers Jr, M B; Hoffman Jr, F J; Morton, J B (1991) Diazepam and haloperidol. Effect on regional brain homovanillic acid levels. Neuropsychopharmacology 5:65-9
Bowers Jr, M B (1991) Characteristics of psychotic inpatients with high or low HVA levels at admission. Am J Psychiatry 148:240-3

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