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Journal of Neuroscience, Vol 9, 2858-2865, Copyright © 1989 by Society for Neuroscience
GABA regulation of circadian responses to light. I. Involvement of GABAA-benzodiazepine and GABAB receptors
MR Ralph and M Menaker
Institute of Neuroscience, University of Oregon, Eugene 97403.
Light-induced phase shifts of the circadian locomotor rhythm of hamsters
can be blocked by agents that alter GABA neurotransmission. The GABA
antagonist bicuculline blocks phase delays induced by light and the
benzodiazepine diazepam, which can potentiate GABA activity, blocks
light-induced phase advances. In the experiments reported here, we found
that the bicuculline blockade of phase delays was reduced by agents that
mimic or potentiate GABA activity. Conversely, the diazepam blockade of
phase advances was reduced by both competitive and noncompetitive
antagonists of GABA. This indicates that the GABA- benzodiazepine
receptor-ionophore complex is the most likely site of action for the
effects of these drugs on circadian rhythms. However, competitive GABA
agonists did not mimic the blocking effects of benzodiazepines, nor did the
antagonist picrotoxin mimic the blocking effect of bicuculline. Therefore,
the classic action of GABA, increased chloride conductance, may not be the
effector mechanism in this case. We also found that the GABAB agonist
baclofen blocked both phase advances and delays and that the blockade of
advances was reversed by the antagonist delta-aminovaleric acid. Taken
together, these results indicate that GABA is involved in the regulation of
circadian responses to light and that the regulation is mediated by both
GABAA and GABAB receptors.
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