Circadian clock speed increases during aging in the male Syrian hamster: A large-scale study.

There are conflicting reports in the literature as to whether or not the circadian period in Syrian hamsters shortens with age, and those studies were conducted with small sample sizes. This report mines data from a large number of experiments resulting in more than 1000 measurements of circadian period in hamsters during aging up to 6 months, and this was correlated with both age and weight. Circadian period was calculated while hamsters were in running wheels in constant darkness.

Non-peptide oxytocin receptor ligands and hamster circadian wheel running rhythms.

The synchronization of circadian rhythms in sleep, endocrine and metabolic functions with the environmental light cycle is essential for health, and dysfunction of this synchrony is thought to play a part in the development of many neurological disorders. There is a demonstrable need to develop new therapeutics for the treatment of neurological disorders such as depression and schizophrenia, and oxytocin is currently being investigated for this purpose. There are no published reports describing activity of oxytocin receptor ligands on mammalian circadian rhythms and that, then, is the purpose of this study.

Effects of systemically applied nAChRα7 agonists and antagonists on light-induced phase shifts of hamster circadian activity rhythms.

Many physiological systems in mammals are linked to the body's master circadian rhythm in the sleep/wake cycle and dysfunctions in this rhythm has been associated with neurological diseases such as major depression, Alzheimer's Disease and schizophrenia. There is some evidence that nicotinic cholinergic input to the master circadian pacemaker, the suprachiasmatic nucleus, may modulate circadian activity rhythms, but data employing in vivo preparations is sparse. Therefore we examined the ability of intraperitoneally applied nicotinic agonists and antagonists relatively selective for the α7 nicotinic receptor to modulate light-induced phase shifts of hamster circadian wheel running rhythms.

LY2033298, a positive allosteric modulator at muscarinic M₄ receptors, enhances inhibition by oxotremorine of light-induced phase shifts in hamster circadian activity rhythms.

Rationale: Entrainment of circadian rhythms to the light-dark cycle is essential for restorative sleep, and abnormal sleep timing is implicated in central nervous system (CNS) disorders like depression, schizophrenia, and Alzheimer's disease. Many transmitters, including acetylcholine, that exerts its actions via muscarinic receptors modulate the suprachiasmatic nucleus, the master pacemaker.

Objectives: Since positive allosteric modulators of muscarinic M(4) receptors are candidates for treatment of mood and cognitive deficits of CNS disorders, it is important to evaluate their circadian actions.

Positive allosteric modulators at GABAB receptors exert intrinsic actions and enhance the influence of baclofen on light-induced phase shifts of hamster circadian activity rhythms.

Light-induced phase shifts of hamster circadian activity rhythms are modulated by GABA(B) receptors. Recently, positive allosteric modulators (PAM)s at GABA(B) receptors were described, but it is not known whether they affect light-induced entrainment of circadian rhythms. Therefore, we studied the effects of two GABA(B) PAMs, GS39783 and RacBHFF, upon light-induced phase advances and delays of hamster circadian wheel-running activity rhythms.

The benzodiazepine diazepam demonstrates the usefulness of Syrian hamsters as a model for anxiety testing: evaluation of other classes of anxiolytics in comparison to diazepam.

Clinical evidence in humans suggests that there is some linkage between dysfunction in the timing of circadian rhythms and certain types of depression. In animal models, Syrian hamsters have been used extensively to study the pharmacology of circadian rhythms, while rats and mice are used to screen putative anxiolytics/antidepressant compounds. It would be beneficial to be able to test anxiolytic/antidepressant compounds in hamsters in conjunction with circadian rhythm studies.

Positive and negative modulation of circadian activity rhythms by mGluR5 and mGluR2/3 metabotropic glutamate receptors.

Glutamate released from retinal ganglion cells conveys information about the daily light:dark cycle to master circadian pacemaker neurons within the suprachiasmatic nucleus that then synchronize internal circadian rhythms with the external day-length. Glutamate activation of ionotropic glutamate receptors in the suprachiasmatic nucleus is well established, but the function of the metabotropic glutamate receptors that are also located in this nucleus is not known. Therefore, in this study we evaluated agonists and antagonists acting at orthosteric or allosteric sites for mGluR5 and mGluR2/3 metabotropic glutamate receptors for their ability to modulate light-induced phase advances and delays of hamster circadian activity rhythms.

Differential influence of selective 5-HT5A vs 5-HT1A, 5-HT1B, or 5-HT2C receptor blockade upon light-induced phase shifts in circadian activity rhythms: interaction studies with citalopram.

Though serotonergic mechanisms modulate circadian rhythms, roles of individual serotonin (5-HT) receptors remain uncertain since data are lacking for antagonists. Herein, both the 5-HT(5A) receptor antagonist, A843277 (10 mg/kg), and the 5-HT(1B) antagonist, SB224289 (1 mg/kg), inhibited light-induced phase advances in hamster circadian wheel-running rhythms. Conversely, though 5-HT(1A) and 5-HT(7) receptors are likewise implicated in circadian scheduling, their blockade by WAY100635 (0.

Serotonin1A-mediated amplification of light-induced phase advances of circadian rhythms in the Syrian hamster: post-light effects.

Certain serotonergic compounds that have an agonist/antagonist activity at the 5-HT(1A) receptor subtype are known to greatly potentiate the ability of light to advance the phase of circadian activity rhythms in hamsters. Typically, investigational compounds are injected 30 min to 1 h prior to a phase-advancing light pulse, and it is not known if these compounds are efficacious when injected after a short light pulse. In this study we injected the 5-HT(1A) mixed agonist/antagonist BMY 7378 from 1 to 7 h after a short phase advancing light pulse at CT 19 in hamsters to assess the temporal window of efficacy of this compound.

Neurokinin1 antagonists potentiate antidepressant properties of serotonin reuptake inhibitors, yet blunt their anxiogenic actions: a neurochemical, electrophysiological, and behavioral characterization.

Though neurokinin(1) (NK(1)) receptor antagonists are active in experimental models of depression, clinical efficacy has proven disappointing. This encourages interest in association of NK(1) receptor blockade with inhibition of serotonin (5-HT) reuptake. The selective NK(1) antagonist, GR205171, dose-dependently enhanced citalopram-induced elevations of extracellular levels of 5-HT in frontal cortex, an action expressed stereospecifically vs its less active distomer, GR226206.

Cannabinoids and hamster circadian activity rhythms.

Circadian activity rhythms in hamsters are entrained to the daily light:dark cycle by photic information arriving from the retina to the suprachiasmatic nucleus, the site of the master circadian pacemaker in mammals. The effects of light on adjusting the timing of the circadian pacemaker is modified, both positively and negatively, by a variety of transmitter systems, but the effects of endocannabinoids have not been reported. Therefore, in this study we evaluated cannabinoids specific for the cannabinoid type 1 receptor (CB(1)) for their ability to modulate light-induced phase advances in hamster circadian activity rhythms.

Evaluation of serotonin, noradrenaline and dopamine reuptake inhibitors on light-induced phase advances in hamster circadian activity rhythms.

Rationale: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for the treatment of anxiodepressive states that are often associated with perturbed circadian rhythms including, in certain patients, phase advances. Surprisingly, the influence of SSRIs upon circadian activity rhythms has been little studied in experimental models.

Objectives: Accordingly, this study examined the ability of SSRIs to modulate the phase-setting properties of light on circadian activity rhythms in hamsters.

The corticotropin-releasing factor (CRF)(1) receptor antagonists CP154,526 and DMP695 inhibit light-induced phase advances of hamster circadian activity rhythms.

The circadian activity of corticotropin releasing factor (CRF) and the hypothalamic-pituitary-adrenal axis is controlled by the master circadian pacemaker located in the hypothalamic suprachiasmatic nucleus. However, the reciprocal influence of CRF and the hypothalamic-pituitary-adrenal axis upon the circadian pacemaker is less well established. Therefore, in the present study, we tested two nonpeptidergic antagonists at CRF(1) receptors for their ability to modulate photic resetting of pacemaker time (phase).

The selective tachykinin neurokinin 1 (NK1) receptor antagonist, GR 205,171, stereospecifically inhibits light-induced phase advances of hamster circadian activity rhythms.

Circadian rhythms in mammals are generated by master pacemaker cells located within the suprachiasmatic nucleus of the hypothalamus. In hamsters, the suprachiasmatic nucleus contains a small collection of cells immunoreactive for substance P, the endogenous ligand of tachykinin neurokinin 1 (NK1) receptors. In addition, two other nuclei which form part of the circadian system, the intergeniculate leaflet of the thalamus and the raphe nuclei, also contain fibers and/or cell bodies immunoreactive for substance P.

Expression of the transcriptional coactivators CBP and p300 in the hamster suprachiasmatic nucleus: possible molecular components of the mammalian circadian clock.

Immediate early genes are expressed in the mammalian suprachiasmatic nucleus in response to photic information arriving from the retina at restricted times of the day, therefore their expression is regulated by the circadian biological clock. These light-induced genes are also activated by the phosphorylated form of CREB (pCREB) that binds to a cAMP response element upstream of the genes. The nuclear proteins CBP and p300 are known to be coactivators with pCREB in certain cell types, but their identification within the rodent SCN has not been reported.

Delta opioid inhibition of light-induced phase advances in hamster circadian activity rhythms.

A master neuronal pacemaker located within the suprachiasmatic nucleus in the ventral hypothalamus generates circadian activity rhythms in hamsters. The circadian pacemaker receives afferent input from many brain regions, one of which is the intergeniculate leaflet of the thalamus. This thalamic input to the suprachiasmatic nucleus in hamsters contains enkephalins, neuropeptide Y, neurotensin, and GABA.