Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus.
Triazolam reportedly causes phase advances in hamster wheel-running rhythm after injection during subjective daytime. However, it is unclear whether benzodiazepine affects the PER: gene expression accompanying a behavioural phase shift. Brotizolam (0.5 - 10 mg kg(-1)) induced large phase advances in hamster rhythm when injected during mid-subjective daytime (circadian time 6 or 9), but not at circadian time 0, 3 or 15. Brotizolam (5 mg kg(-1)) significantly reduced the expression of PER:1 and PER:2 in the suprachiasmatic nucleus 1 and 2 h after injection at circadian time 6, and slightly reduced them at circadian time 20. Injection of 8-OH-DPAT (5 mg kg(-1)) at subjective daytime induced similar phase advances with a reduction of PER:1 and PER:2 expression. Co-administration of brotizolam with 8-OH DPAT failed to potentiate the 8-OH DPAT-induced phase advances and reduced PER: expression. Both phase advance and rapid induction of PER:1 and PER:2 in the suprachiasmatic nucleus after light exposure (5 lux, 15 min) at circadian time 20 was strongly attenuated by co-treatment with brotizolam 5 mg kg(-1). The present results strongly suggest that reduction of PER:1 and/or PER:2 expression during subjective daytime by brotizolam may be an important step in causing a behavioural phase advance. The co-administration experiment suggests that common mechanism(s) are involved in brotizolam- or 8-OH DPAT-induced phase advances and the reduction of PER: gene expression. These results suggest that brotizolam is not only a good drug for insomnia but also a drug capable of facilitating re-entrainment like melatonin.
Yokota
S I
SI
Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Tokorozawa, Saitama 359-1192, Japan.
Horikawa
K
K
Akiyama
M
M
Moriya
T
T
Ebihara
S
S
Komuro
G
G
Ohta
T
T
Shibata
S
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D017403:In Situ Hybridization; D008027:Light; D008297:Male; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013493:Suprachiasmatic Nucleus / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors
D001381:Azepines; D018797:Cell Cycle Proteins; D006993:Hypnotics and Sedatives; D009687:Nuclear Proteins; C513312:Per2 protein, mouse; C512645:Per3 protein, mouse; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors; C020960:brotizolam; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin