M.D., Hahnemann University, 1983
Assistant Professor
Department of Psychiatry and Human Behavior
Research Service, VA Medical Center
Tel. (401) 457-3066
M.D., Hahnemann University, 1983
Assistant
Professor
Department of Psychiatry and Human Behavior
Research
Service, VA Medical Center
Tel. (401) 457-3066
The goals of our research are to better understand the neurobiological
mechanisms which mediate psychoactive drug effects and to develop new treatments
for psychiatric disorders, such as drug dependence and depression. We are
studying signal transduction, the process by which a psychoactive drug exerts
its cellular and ultimately behavioral effects. Drugs act as first messengers,
binding to and changing the shape of cell surface receptors in neurons. These
ligand -receptor binding interactions produce a cascade of additional molecular
events resulting in the transmission of the signal throughout the cell.
Receptor activation results in stimulation of a transducing agent (G protein)
which in turn activates effector enzymes (e.g. adenylate cyclase). These
effectors can amplify the extracellular signals by producing large amounts of
second messengers (e.g. cAMP) which act upon intracellular targets, such as
protein kinases. Protein kinases then phosphorylate cellular proteins and alter
neuronal cellular function. These drug-induced biochemical changes produce
physiological and behavioral responses as wide ranging as drug dependence and
antidepressant efficacy. In our lab, we are specifically examining the
receptor, second messenger, G protein and protein kinase mechanisms which
mediate behavioral effects of psychotropic agents such as opiates, caffeine and
antidepressants.
Kaplan, B.B., Leite-Morris, K.A. and Sears, M.T. (1994) Alterations
in adenosine A1 receptors in morphine dependence. Brain Res.
657: 347-350.
Kaplan, G.B., Kent, M.A., Cotreau-Bibbo, M.M. and Greenblatt,
D.J. (1993) Caffeine treatment and withdrawal in mice: Relationships between
dosage, concentrations, locomotor activity and A1 adensosine
receptor binding.
J. Pharmacol. Exp. Ther. 266: 1563-1572.
Kaplan, G.B., Greenblatt,
D.J., Kent, M.A., Cotreau, M.M., Arcelin, G., Shader, R.I. (1992).
Caffeine-induced behavioral stimulation is dose-dependent and associated with A1
adenosine receptor occupancy. Neuropsychopharmacology 6:145-153.
Kaplan, G.B., Cotreau, M.M., Greenblatt, D.J. (1992). Effects of benzodiazepine
administration on A1 adenosine receptor binding in vivo and
ex vivo. J. Pharm. Pharmacol. 44:700-703.
Significant effects of chronic morphine (vs. vehicle) on G protein (GTP analogue)-stimulated adenylate cyclase (top) and adenosine A2a agonist-stimulated adenylate cyclase (bottom) from striatal tissues of treated mice.