title: Facilitation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor transmission in the suprachiasmatic nucleus by aniracetam enhances photic responses of the biological clock in rodents.
abstract: This study was designed to test whether the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-facilitating drug, aniracetam, could potentiate photic responses of the biological clock in the suprachiasmatic nucleus (SCN) of rodents. Using the whole-cell patch technique, we first demonstrated that AMPA currents elicited by either local AMPA application or optic chiasm stimulation were augmented by aniracetam in the neurons of the SCN. The AMPA application-elicited increase of intracellular Ca2+ concentration in SCN slices was also enhanced by aniracetam treatment. The systemic injection of aniracetam dose-dependently (10-100 mg/kg) potentiated the phase delay in behavioral rhythm induced by brief light exposure of low intensity (3 lux) but not high intensity (10 or 60 lux) during early subjective night. Under the blockade of NMDA receptors by (+) MK801, aniracetam failed to potentiate a light (3 lux)-induced phase delay in behavioral rhythm. Aniracetam increased the photic induction of c-Fos protein in the SCN that was elicited by low intensity light exposure (3 lux). These results suggest that AMPA receptor-mediated responses facilitated by aniracetam can explain enhanced photic responses of the biological clock in the SCN of rodents.
authors.affiliation: Departments of Pharmacology and Brain Science, School of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa-shi, Saitama 359-1192, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Moriya
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ikeda
authors.forename: Koji
authors.initials: K
authors.lastname: Teshima
authors.forename: Reiko
authors.initials: R
authors.lastname: Hara
authors.forename: Koji
authors.initials: K
authors.lastname: Kuriyama
authors.forename: Tohru
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Charles N
authors.initials: CN
authors.lastname: Allen
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001683:Biological Clocks / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation / Q000379:methods; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D018691:Excitatory Amino Acid Antagonists; D005456:Fluorescent Dyes; D018697:Nootropic Agents; D016760:Proto-Oncogene Proteins c-fos; D011760:Pyrrolidinones; D018091:Receptors, AMPA; C036466:aniracetam; D002118:Calcium