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

  • Smith R
  • Turek F
  • Traverse Slater N
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Permanent phase shifts in the free-running rhythm of locomotor activity of the golden hamster were induced with microinjections of the γ-aminobutyric acid (GABA) agonists muscimol of baclofen in the hypothalamic suprachiasmatic nuclei. Muscimol and baclofen exhibit relatively high binding affinities for GABAAand GABABreceptors, respectively. Microinjections of the GABA antagonists, bicuculline methobromide or picrotoxinin, thought to block the actions of GABA at GABAAreceptors, could block phase shifts induced by muscimol but not the benzodiazepine, triazolam. Microinjections of the postsynaptic GABABreceptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABABreceptor 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 GABAAand GABABreceptors 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. © 1990.

Author-supplied keywords

  • Baclofen
  • Bicuculline
  • Circadian
  • Muscimol
  • Phaclofen
  • Picrotoxin
  • Suprachiasmatic nucleus
  • γ-Aminobutyric acid

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  • Richard D. Smith

  • Fred W. Turek

  • N. Traverse Slater

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