Bicuculline and picrotoxin block phase advances induced by GABA agonists in the circadian rhythm of locomotor activity in the golden hamster by a phaclofen-insensitive mechanism.
Permanent phase shifts in the free-running rhythm of locomotor activity of the golden hamster were induced with microinjections of the gamma-aminobutyric acid (GABA) agonists muscimol or baclofen in the hypothalamic suprachiasmatic nuclei. Muscimol and baclofen exhibit relatively high binding affinities for GABAA and GABAB receptors, respectively. Microinjections of the GABA antagonists, bicuculline methobromide or picrotoxinin, thought to block the actions of GABA at GABAA receptors, could block phase shifts induced by muscimol but not the benzodiazepine, triazolam. Microinjections of the postsynaptic GABAB receptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABAB receptor sites, did not block the phase-shifting actions of either muscimol or baclofen. GABAergic antagonists when given alone did not induce phase shifts. Collectively, these studies indicate that when activated by exogenous GABAergic agents, a GABAergic system associated with both GABAA and GABAB receptors exists as a neural regulatory mechanism that can reset the mammalian circadian clock. However, GABAergic synaptic pathways may not be normally involved in the circadian timing system.
Smith
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RD
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.
Turek
F W
FW
Slater
N T
NT
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001640:Bicuculline / Q000008:administration & dosage / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects*; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009118:Muscimol / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*; D013238:Stereotaxic Techniques; D014229:Triazolam / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001418:Baclofen; D001640:Bicuculline; D009118:Muscimol; D010852:Picrotoxin; D014229:Triazolam; D005680:gamma-Aminobutyric Acid; C052329:phaclofen