GABA regulation of circadian responses to light. I. Involvement of GABAA-benzodiazepine and GABAB receptors.
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.
Ralph
M R
MR
Institute of Neuroscience, University of Oregon, Eugene 97403.
Menaker
M
M
D000596:Amino Acids / Q000494:pharmacology; D021542:Amino Acids, Neutral; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects; D006224:Cricetinae; D018756:GABA Antagonists; D008027:Light; D008297:Male; D008647:Mesocricetus; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000596:Amino Acids; D021542:Amino Acids, Neutral; D018756:GABA Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C013809:5-aminovaleric acid; D001418:Baclofen