Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands

Djeridane, Yasmina; Touitou, Yvan

doi:10.1007/s002130000631

Cited by 21 publications

(10 citation statements)

References 22 publications

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“…Animal studies have indicated that benzodiazepines may also affect sleep by inhibiting melatonin synthesis by the pineal gland. 50 Both lorazepam and midazolam, the most commonly used benzodiazepines in the ICU, have been shown to be strong independent risk factors for the development of delirium. 51;52 Whether the increased incidence of delirium occurring with benzodiazepine use is secondary to primary effects on sleep (decreased SWS and REM sleep), to changes in neurotransmitter imbalance (ongoing release of norepinephrine from the LC), or to other mechanisms remains to be determined.…”

Section: Sedation Sleep and Deliriummentioning

confidence: 99%

Delirium: Is sleep important?

Watson

Ceriana

Fanfulla

2012

Best Practice & Research Clinical Anaesthesiology

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Delirium and poor sleep quality are common and often co-exist in hospitalized patients. A link between these disorders has been hypothesized but whether this link is a cause and effect relationship or simply an association resulting from shared mechanisms is yet to be determined. Potential shared mechanisms include: abnormalities of neurotransmitters, tissue ischemia, inflammation, and sedative exposure. Sedatives, while decreasing sleep latency, often cause a decrease in slow wave sleep and stage REM sleep and therefore may not provide the same restorative properties as natural sleep. Mechanical ventilation, an important cause of sleep disruption in ICU patients, may lead to sleep disruption not only from the discomfort of the endotracheal tube but also as a result of ineffective respiratory efforts and by inducing central apnea events if not properly adjusted for the patient’s physiologic needs. When possible, efforts should be made to optimize the patient-ventilator interaction to minimize sleep disruptions.

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Section: Sedation Sleep and Deliriummentioning

confidence: 99%

Delirium: Is sleep important?

Watson

Ceriana

Fanfulla

2012

Best Practice & Research Clinical Anaesthesiology

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“…The dose of diazepam and time of drug administration were chosen according to previously published data (Wakabayashi et al, 1991b;Mailliet et al, 2001;Djeridane and Touitou, 2001). Control animals (n ¼ 5) received only aqueous vehicle (Roche) equal in volume to the diazepam solution administered to experimental animals.…”

Section: Animals and Experimental Proceduresmentioning

confidence: 99%

Diazepam affects both level and amplitude of rat locomotor activity rhythm but has no effect on core body temperature

Djeridane

Touitou

2005

Chronobiology International

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The present study investigates the effects of a chronic administration of diazepam, a benzodiazepine widely used as an anxiolytic, on locomotor activity and body core temperature rhythms in male Wistar rats housed under 12 : 12 light : dark (LD) cycle conditions. Diazepam was administered subcutaneously for 3 wks in a dosage of 3 mg/kg body weight/day, 1 h before the onset of darkness. Diazepam increased the level of locomotor activity from the first day until the end of treatment, and also increased the amplitude of the activity circadian rhythm, but only on the third wk of treatment. Diazepam exerted no effects on the length of the period and did not affect the phase of the locomotor activity rhythm. The body temperature rhythm of rats was affected neither by short-term (a single injection) nor by long-term (every day for 3 wks) diazepam treatment. Diazepam lacked effect on body core temperature even on the first day of administration, thereby ruling out the possibility of drug tolerance development. The fact that diazepam affects locomotor activity, but not core body temperature, suggests that different mechanisms mediate the actions of diazepam on locomotor activity and on core body temperature.

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“…MEL seems to reduce de-pendence and tolerance caused by chronic use of BZD [25]. Many observations seem to support this direction: 1) BZD binding sites were identified in the pineal gland and in the rat removal of the gland abolishes the diurnal variation of BZD binding sites in the cerebral cortex; 2) in humans BZD may potentiate inhibitory effect of GABA on MEL synthesis, which in turn induces changes in function of GABA receptors and BZD; and 3) in vivo, diazepam (DZ) induces strong inhibition of MEL production, by acting directly on AA-NAT, limiting factor of MEL synthesis [26,27]. Furthermore, in rats, chronic treatment with DZ causes the disappearance of MEL binding sites in the "pons medulla".…”

Section: Introductionmentioning

confidence: 99%

Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

Ouakki¹,

Mrabet²,

Lagbouri³

et al. 2013

JBBS

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Recent studies have shown the importance of the GABA-ergic transmission in the pathophysiology of anxiety and depressive disorders in humans. Our present study aims to investigate the interaction of melatonin (MEL) with this system by exploring the effects of MEL with or without a facilitator of GABA-ergic neurotransmission, diazepam (DZ) on the levels of depression and anxiety in Wistar rats. For this purpose, different doses of MEL (2, 4 or 16 mg/kg) or DZ (2 mg/kg) are subchronically administered during 15 days. After pharmacological treatments, anxiety levels are evaluated in behavioral tests of Open Field (OFT) and elevated plus maze (EPM) and depression levels are evaluated by the forced swim test (FST). The results showed that MEL produces anxiolytic-like and antidepressant-like effects in a dosedependent manner; the maximum effect was obtained at a dose of 16 mg/kg. However, a dose of 4 mg/kg is necessary to induce an effect. The effect of MEL and DZ reported in this study concerns selective modulation of behavioral anxiety and depression since locomotor activity assessed by the OFT and EPM was not affected. The subchronic injection of MEL at 4 mg/kg, DZ at 2 mg/kg or the two combined molecules also induces also anxiety-like and antidepressant-like behavior. In addition, a potentiating effect between MEL and DZ was observed. These effects suggest that psychopharmacological actions of MEL are due, at least in part, to its ability to improve the central GABA-ergic transmission.

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Chronic diazepam administration differentially affects melatonin synthesis in rat pineal and Harderian glands

Cited by 21 publications

References 22 publications

Delirium: Is sleep important?

Delirium: Is sleep important?

Diazepam affects both level and amplitude of rat locomotor activity rhythm but has no effect on core body temperature

Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission

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