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Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus.

ABSTRACT: 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.

SUBMITTER: Yokota SI

PROVIDER: S-EPMC1572494 | biostudies-literature | 2000 Dec

REPOSITORIES: biostudies-literature

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Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus.

Yokota S I SI Horikawa K K Akiyama M M Moriya T T Ebihara S S Komuro G G Ohta T T Shibata S S

British journal of pharmacology 20001201 8

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 PE ...[more]

PMID: 11139454

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Project description:The suprachiasmatic nuclei (SCN) host a robust, self-sustained circadian pacemaker that coordinates physiological rhythms with the daily changes in the environment. Neuronal clocks within the SCN form a heterogeneous network that must synchronize to maintain timekeeping activity. Coherent circadian output of the SCN tissue is established by intercellular signaling factors, such as vasointestinal polypeptide. It was recently shown that besides coordinating cells, the synchronization factors play a crucial role in the sustenance of intrinsic cellular rhythmicity. Disruption of intercellular signaling abolishes sustained rhythmicity in a majority of neurons and desynchronizes the remaining rhythmic neurons. Based on these observations, the authors propose a model for the synchronization of circadian oscillators that combines intracellular and intercellular dynamics at the single-cell level. The model is a heterogeneous network of circadian neuronal oscillators where individual oscillators are damped rather than self-sustained. The authors simulated different experimental conditions and found that: (1) in normal, constant conditions, coupled circadian oscillators quickly synchronize and produce a coherent output; (2) in large populations, such oscillators either synchronize or gradually lose rhythmicity, but do not run out of phase, demonstrating that rhythmicity and synchrony are codependent; (3) the number of oscillators and connectivity are important for these synchronization properties; (4) slow oscillators have a higher impact on the period in mixed populations; and (5) coupled circadian oscillators can be efficiently entrained by light-dark cycles. Based on these results, it is predicted that: (1) a majority of SCN neurons needs periodic synchronization signal to be rhythmic; (2) a small number of neurons or a low connectivity results in desynchrony; and (3) amplitudes and phases of neurons are negatively correlated. The authors conclude that to understand the orchestration of timekeeping in the SCN, intracellular circadian clocks cannot be isolated from their intercellular communication components.

Dataset Information

Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus.

Publications

Inhibitory action of brotizolam on circadian and light-induced per1 and per2 expression in the hamster suprachiasmatic nucleus.

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