Lithium is a psychiatrically important agent that is widely used to alleviate the symptoms of affective disorders. The mechanisms of action of this agent in the central nervous system are not well understood. Our preliminary data show that lithium potentiates the modulatory actions of acetylcholine on hippocampal excitatory and inhibitory synaptic transmission. The broad goal of this study is to begin to define mechanisms by which lithium may produce its clinical effects. Using the techniques of electrophysiological recording in the in vitro hippocampal brain slice preparation, we have shown in preliminary results that cholinergic agonists depress both excitatory and inhibitory synaptic transmission. Application of lithium to the hippocampal slices, at clinically relevant concentrations, significantly potentiates these cholinergic effects. We propose to use a variety of electrophysiological recording techniques and pharmacological probes to identify neuronal sites of action of lithium. We believe this will provide significant information toward defining the mechanisms of action of this clinically important agent.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH048874-03
Application #
2248432
Study Section
Neurosciences Research Review Committee (BPN)
Project Start
1992-03-01
Project End
1997-02-28
Budget Start
1994-04-01
Budget End
1995-02-28
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Stanford University
Department
Biophysics
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305