Regulation of tissue regeneration by the circadian clock.

Circadian rhythms are regulated by a highly conserved transcriptional/translational feedback loop that maintains approximately 24-hr periodicity from cellular to organismal levels. Much research effort is being devoted to understanding how the outputs of the master clock affect peripheral oscillators, and in turn, numerous biological processes. Recent studies have revealed roles for circadian timing in the regulation of numerous cellular behaviours in support of complex tissue regeneration.

Photoresponsivity and motility in the planarian vary diurnally.

The planarian flatworm has become one of the leading animal model systems for studying stem cell behavior and tissue regeneration. Recent studies have shown that components of the circadian clockwork have important roles in tissue homeostasis and repair. However, it remains unknown whether planarians exhibit circadian or diurnal rhythms in physiology or behavior.

Sex Differences in Photic Entrainment and Sensitivity to Ethanol-Induced Chronodisruption in Adult Mice After Adolescent Intermittent Ethanol Exposure.

Background: Evidence supports a role for the circadian system in alcohol use disorders, but the impact of adolescent alcohol exposure on circadian timing later in life is unknown. Acute ethanol (EtOH) attenuates circadian photic phase-resetting in adult, but not adolescent, rodents. However, nearly all studies have focused on males and it is unknown whether this adolescent-typical insensitivity to EtOH persists into adulthood after adolescent drinking.

Caffeine Delays Light-entrained Activity and Potentiates Circadian Photic Phase-resetting in Mice.

Caffeine is widely used to reduce sedation and increase alertness. However, long-term caffeine use may disrupt circadian (daily, 24-h) rhythms and thereby negatively affect health. Here, we examined the effect of caffeine on photic regulation of circadian activity rhythms in mice.

Differential Sensitivity to Ethanol-Induced Circadian Rhythm Disruption in Adolescent and Adult Mice.

Background: Growing evidence supports a central role for the circadian system in alcohol use disorders, but few studies have examined this relationship during adolescence. In mammals, circadian rhythms are regulated by the suprachiasmatic nucleus, a biological clock whose timing is synchronized (reset) to the environment primarily by light (photic) input. Alcohol (ethanol [EtOH]) disrupts circadian timing in part by attenuating photic phase-resetting responses in adult rodents.

Lateral hypothalamic kindling induces manic-like behavior in rats: a novel animal model.

The lateral hypothalamus integrates critical physiological functions such as the sleep-wake cycle, energy expenditure, and sexual behaviors. These functions are severely dysregulated during mania. In this study, we successfully induced manic-like behavioral phenotypes in adult, male Wistar rats through bilateral lateral hypothalamic area kindling (LHK).

Adenosine and glutamate in neuroglial interaction: implications for circadian disorders and alcoholism.

Recent studies have demonstrated that the function of glia is not restricted to the support of neuronal function. In fact, astrocytes are essential for neuronal activity in the brain and play an important role in the regulation of complex behavior. Astrocytes actively participate in synapse formation and brain information processing by releasing and uptaking glutamate, D-serine, adenosine 5'-triphosphate (ATP), and adenosine.

Activation of neurotensin receptor type 1 attenuates locomotor activity.

Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we investigated the effect of systemic and brain region-specific NTS1 activation on locomotor activity.

Adenosinergic regulation of striatal clock gene expression and ethanol intake during constant light.

Circadian rhythm and sleep disruptions occur frequently in individuals with alcohol use disorders (AUD) and present significant barriers to treatment. Recently, a variant of adenosine transporter, equilibrative nucleoside transporter 1 (ENT1), was associated with the co-occurrence of sleep problems and AUD. We have previously shown that mice lacking ENT1 (ENT1 KO) have reduced adenosine levels in the striatum and drink more alcohol compared with wild types (WT).

Attenuation of ethanol withdrawal by ceftriaxone-induced upregulation of glutamate transporter EAAT2.

Alcohol withdrawal syndrome (AWS) is a potentially fatal outcome of severe alcohol dependence that presents a significant challenge to treatment. Although AWS is thought to be driven by a hyperglutamatergic brain state, benzodiazepines, which target the GABAergic system, comprise the first line of treatment for AWS. Using a rat model of ethanol withdrawal, we tested whether ceftriaxone, a β-lactam antibiotic known to increase the expression and activity of glutamate uptake transporter EAAT2, reduces the occurrence or severity of ethanol withdrawal manifestations.

Adenosine transporter ENT1 regulates the acquisition of goal-directed behavior and ethanol drinking through A2A receptor in the dorsomedial striatum.

Adenosine signaling has been implicated in the pathophysiology of many psychiatric disorders including alcoholism. Striatal adenosine A2A receptors (A2AR) play an essential role in both ethanol drinking and the shift from goal-directed action to habitual behavior. However, direct evidence for a role of striatal A2AR signaling in ethanol drinking and habit development has not been established.

Sex-Specific Regulation of Depression, Anxiety-Like Behaviors and Alcohol Drinking in Mice Lacking ENT1.

OBJECTIVES: Adenosine signaling has been implicated in the pathophysiology of several psychiatric disorders including alcoholism, depression, and anxiety. Adenosine levels are controlled in part by transport across the cell membrane by equilibrative nucleoside transporters (ENTs). Recent evidence showed that a polymorphism in the gene encoding ENT1 is associated with comorbid depression and alcoholism in women.

Striatal adenosine signaling regulates EAAT2 and astrocytic AQP4 expression and alcohol drinking in mice.

Adenosine signaling is implicated in several neuropsychiatric disorders, including alcoholism. Among its diverse functions in the brain, adenosine regulates glutamate release and has an essential role in ethanol sensitivity and preference. However, the molecular mechanisms underlying adenosine-mediated glutamate signaling in neuroglial interaction remain elusive.

Acute ethanol disrupts photic and serotonergic circadian clock phase-resetting in the mouse.

Background: Alcohol dependence is associated with impaired circadian rhythms and sleep. Ethanol administration disrupts circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol dependence on the circadian timing system. In this study, we extend previous work in C57BL/6J mice to: (i) characterize the suprachiasmatic nucleus (SCN) pharmacokinetics of acute systemic ethanol administration, (ii) explore the effects of acute ethanol on photic and nonphotic phase-resetting, and (iii) determine if the SCN is a direct target for photic effects.

An essential role for adenosine signaling in alcohol abuse.

In the central nervous system (CNS), adenosine plays an important role in regulating neuronal activity and modulates signaling by other neurotransmitters, including GABA, glutamate, and dopamine. Adenosine suppresses neurotransmitter release, reduces neuronal excitability, and regulates ion channel function through activation of four classes of G protein-coupled receptors, A(1), A(2A), A(2B), and A(3). Central adenosine are largely controlled by nucleoside transporters, which transport adenosine levels across the plasma membrane.

Environmental modulation of alcohol intake in hamsters: effects of wheel running and constant light exposure.

Background: Alcohol abuse leads to marked disruptions of circadian rhythms, and these disturbances in themselves can increase the drive to drink. Circadian clock timing is regulated by light, as well as by nonphotic influences such as food, social interactions, and wheel running. We previously reported that alcohol markedly disrupts photic and nonphotic modes of circadian rhythm regulation in Syrian hamsters.

Chronic ethanol disrupts circadian photic entrainment and daily locomotor activity in the mouse.

Background: Chronic ethanol abuse is associated with disrupted circadian rhythms and sleep. Ethanol administration impairs circadian clock phase-resetting, suggesting a mode for the disruptive effect of alcohol abuse on circadian timing. Here, we extend previous studies to explore the effects of chronic forced ethanol on photic phase-resetting, photic entrainment, and daily locomotor activity patterns in C57BL/6J mice.

Chronic ethanol attenuates circadian photic phase resetting and alters nocturnal activity patterns in the hamster.

Acute ethanol (EtOH) administration impairs circadian clock phase resetting, suggesting a mode for the disruptive effect of alcohol abuse on human circadian rhythms. Here, we extend this research by characterizing the chronobiological effects of chronic alcohol consumption. First, daily profiles of EtOH were measured in the suprachiasmatic nucleus (SCN) and subcutaneously using microdialysis in hamsters drinking EtOH.

Acute ethanol impairs photic and nonphotic circadian phase resetting in the Syrian hamster.

Disrupted circadian rhythmicity is associated with ethanol (EtOH) abuse, yet little is known about how EtOH affects the mammalian circadian clock of the suprachiasmatic nucleus (SCN). Clock timing is regulated by photic and nonphotic inputs to the SCN involving glutamate release from the retinohypothalamic tract and serotonin (5-HT) from the midbrain raphe, respectively. Our recent in vitro studies in the SCN slice revealed that EtOH blocks photic phase-resetting action of glutamate and enhances the nonphotic phase-resetting action of the 5-HT1A,7 agonist, 8-OH-DPAT.