The goal is to characterize actions of serotonin (5-HT) in the CNS and determine the role of 5-HT in the etiology and treatment of pathological states such as depression. The award of the RSDA would allow the Principal Investigator (P.I.) to learn new electrophysiological and neurochemical techniques and to continue collaborations that extend the scope of the research project beyond electrophysiology.
Specific Aim 1 is to identify the 5-HT receptors and cellular mechanisms underlying the fast transient increase in cell excitability elicited by 5-HT. Both extracellular and intracellular recordings will be used to determine if the excitation is due to: a) presynaptic modulation of neurotransmitter release; b) disinhibition; c) potentiation of glutamate responses or; d) amplification of a voltage dependent cation conductance.
Specific Aim 2 is to determine the G-protein or G-protein submits that link the 5-HT(1A) receptor to potassium channels. To accomplish this, the P.I. will learn whole cell voltage clamp procedures in dissociated cells in the laboratory of Dr. Traverse Slater. Dr. Ravi Iyengar will provide the purified G-proteins and G-protein subunits.
Specific Aim 3 is to determine if activation of 5-HT receptors can augment beta-adrenergic and/or cholinergic receptor mediated responses recorded intracellularly, since receptors that elicit similar cellular responses often share signal transduction mechanisms. Dr. George Battaglia will conduct analogous biochemical experiments to determine if 5-HT augments beta-adrenergic stimulation of adenylyl cyclase activity. Also, the modulation of the beta-adrenergic receptors by 5-HT will be probed following lesions of the 5-HT input to the hippocampus. Dr. Stanley Lorens will teach the P.I. this technique and how to quantitate 5-HT levels by HPLC.
Specific Aim 4 is to determine if distinct classes of antidepressant drugs differentially alter 5-HT and beta-adrenergic receptor- mediated responses. An alteration in the actions of a neurotransmitter by antidepressants may also affect the actions of other neurotransmitters due to shared effector mechanisms. Learning the actions of the drugs on the 5-HT and beta-adrenergic receptors will help elucidate the role of 5-HT, norepinephrine and the hippocampus in depressive illnesses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH000880-05
Application #
2240088
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Loyola University Chicago
Department
Pharmacology
Type
Schools of Medicine
DUNS #
791277940
City
Maywood
State
IL
Country
United States
Zip Code
60153
Okuhara, D Y; Beck, S G (1998) Corticosteroids influence the action potential firing pattern of hippocampal subfield CA3 pyramidal cells. Neuroendocrinology 67:58-66
Okuhara, D Y; Beck, S G (1998) Corticosteroids alter 5-hydroxytryptamine1A receptor-effector pathway in hippocampal subfield CA3 pyramidal cells. J Pharmacol Exp Ther 284:1227-33
Okuhara, D Y; Beck, S G; Muma, N A (1997) Corticosterone alters G protein alpha-subunit levels in the rat hippocampus. Brain Res 745:144-51
Birnstiel, S; Wulfert, E; Beck, S G (1997) Levetiracetam (ucb LO59) affects in vitro models of epilepsy in CA3 pyramidal neurons without altering normal synaptic transmission. Naunyn Schmiedebergs Arch Pharmacol 356:611-8
Beck, S G; Birnstiel, S; Choi, K C et al. (1997) Fluoxetine selectively alters 5-hydroxytryptamine1A and gamma-aminobutyric acidB receptor-mediated hyperpolarization in area CA1, but not area CA3, hippocampal pyramidal cells. J Pharmacol Exp Ther 281:115-22
Okuhara, D Y; Lee, J M; Beck, S G et al. (1996) Differential immunohistochemical labeling of Gs, G(il) and 2, and G(o) alpha-subunits in rat forebrain. Synapse 23:246-57
Kerr, J E; Beck, S G; Handa, R J (1996) Androgens selectively modulate C-fos messenger RNA induction in the rat hippocampus following novelty. Neuroscience 74:757-66
Kerr, J E; Beck, S G; Handa, R J (1996) Androgens modulate glucocorticoid receptor mRNA, but not mineralocorticoid receptor mRNA levels, in the rat hippocampus. J Neuroendocrinol 8:439-47
Beck, S G; Choi, K C; List, T J et al. (1996) Corticosterone alters 5-HT1A receptor-mediated hyperpolarization in area CA1 hippocampal pyramidal neurons. Neuropsychopharmacology 14:27-33
Pouliot, W A; Handa, R J; Beck, S G (1996) Androgen modulates N-methyl-D-aspartate-mediated depolarization in CA1 hippocampal pyramidal cells. Synapse 23:10-9

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