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GABA Receptor-Mediated Inhibition of Neuronal Activity in Rat SCN In Vitro: Pharmacology and Influence of Circadian Phase

¹ Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492 ² Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523

Submitted 2 December 2002; accepted in final form 9 May 2003

The effect of -aminobutyric acid (GABA) on neuronal firing rate in rat suprachiasmatic nucleus (SCN) slices was examined using continuous recording methods. GABA inhibited neuronal discharge during both the subjective day and the subjective night in a concentration-dependent manner characterized by two apparent affinity states. The GABA_A receptor agonist muscimol caused potent inhibition regardless of circadian time; repeated applications of the agonist did not reverse the direction of effect. The GABA_A receptor antagonists bicuculline and picrotoxin increased excitability when applied during either subjective day or subjective night. A significant increase in GABA_A receptor– mediated inhibition, as well as endogenous GABAergic tone, was observed on the second day after slice preparation. The GABA_B receptor agonist baclofen inhibited cell firing during subjective day and night, but the GABA_B 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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