GABA receptor-mediated inhibition of neuronal activity in rat SCN in vitro: pharmacology and influence of circadian phase.
The effect of gamma-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 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 during either subjective day or subjective night. A significant increase in GABAA receptor- mediated inhibition, as well as endogenous GABAergic 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.
Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA. Valentin.Gribkoff@bms.com
Valentin K
VK
Gribkoff
Rick L
RL
Pieschl
F Edward
FE
Dudek
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D018079:Receptors, GABA / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology*
D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA