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J Neurophysiol (May 15, 2003). doi:10.1152/jn.01082.2002
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Submitted on December 2, 2002
Accepted on May 9, 2003

GABA receptor-mediated inhibition of neuronal activity in rat SCN in vitro: Pharmacology and influence of circadian phase

Valentin K. Gribkoff1*, Rick L. Pieschl1, and F. E. Dudek2

1 Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT, USA
2 Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO, USA

* To whom correspondence should be addressed. E-mail: Valentin.Gribkoff{at}bms.com.

The effect of {gamma}-amino butyric acid (GABA) on neuronal firing rate in rat suprachiasmatic nucleus (SCN) slices was examined using continuous recording methods. GABA inhibited neuronal discharge during subjective day and subjective night in a concentration-dependent manner characterized by two apparent affinity states. The GABAA receptor agonist muscimol caused potent inhibition regardless of circadian time; repeated applications of the agonist did not reverse the direction of effect. The GABAA receptor antagonists bicuculline and picrotoxin increased excitability when applied either during subjective day or night. A significant increase in GABAA receptor-mediated responses, as well as endogenous GABA-ergic tone, was observed on the second day after slice preparation. The GABAB receptor agonist baclofen inhibited cell firing during subjective day and night, but the GABAB antagonist phaclofen had no significant effect. These data provide additional strong support for a predominantly inhibitory role of GABA in the rat SCN, regardless of the time of application in relation to the circadian rhythm, and demonstrate an important level of plasticity of this system in vitro.




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