DOCSLIB.ORG

Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption Neuropsychopharmacology (2015) 40, 2897–2906 © 2015 American College of Neuropsychopharmacology. All rights reserved 0893-133X/15 www.neuropsychopharmacology.org Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption ,1 1 1 Valentina Vengeliene* , Hamid R Noori and Rainer Spanagel 1 Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effects on alcohol consumption. We conclude that targeting the melatonergic system in alcohol-dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behavior. Neuropsychopharmacology (2015) 40, 2897–2906; doi:10.1038/npp.2015.143; published online 10 June 2015 INTRODUCTION exposure (Rhodes et al, 2005). On the other hand, alcohol drinking alters the circadian profile of the melatonin Most physiological functions of the body as well as certain production and disturbed circadian rhythms were found in behavioral patterns are synchronized to the presence/absence both alcohol-dependent patients and alcohol drinking rats of the daylight. One of the major players responsible for the (Kühlwein et al, 2003; Peres et al, 2011). Melatonin produces control of our daily rhythms is melatonin. It is a hormone its effects through two melatonin receptors—MT1 and MT2 generally synthesized in the pineal gland during the dark (von Gall et al, 2002). The MT1 receptor protein has been phase of the photoperiod (Lynch et al, 1975). Fluctuating found in several brain regions known to have a crucial role in levels of melatonin tunes cellular activity throughout the body mediating the effects of drugs and addictive behavior, such as to the actual time-of-day. High melatonin levels reinforce prefrontal cortex, striatum, nucleus accumbens, amygdala, physiological functions and behaviors associated with the and hippocampus (Uz et al, 2005; Noori et al, 2012). darkness, whereas low levels have the opposite effect. The aim of our study was to investigate whether the Research on the interaction between alcohol and circadian melatonin system could be used as a target to treat alcohol rhythms started several decades ago. This interaction is addiction. For this purpose we used male Wistar rats bidirectional. On one hand, behavioral and physiological subjected to long-term voluntary alcohol consumption in a responses to alcohol as well as alcohol preference depend on four-bottle procedure, repeatedly interrupted with the the time-of-day (Brick et al, 1984). Rats maintained in total abstinence phases. In rats that had long-term voluntary darkness drink more alcohol than those kept under constant access to alcohol followed by deprivation for several weeks, illumination (Geller 1971), and an animal model called — ‘ ’ the re-presentation of alcohol leads to relapse-like drinking drinking in the dark is in fact based on the timing of alcohol a temporal increase in alcohol intake over the baseline drinking. This robust phenomenon is called the alcohol *Correspondence: Dr V Vengeliene, Institute of Psychopharmacology, deprivation effect (ADE; Sinclair and Senter, 1967; Spanagel Central Institute of Mental Health (CIMH), Medical Faculty Mannheim/University of Heidelberg, J5, Mannheim, 68159, Germany, and Hölter, 1999). Our previous research has demonstrated Tel: +49 621 1703 6261, Fax: +49 621 1703 6255, that alcohol consumption during these post-abstinence E-mail: [email protected] drinking days is characterized by an increased frequency of Received 6 February 2015; revised 24 April 2015; accepted 15 May approaches to the alcohol bottles, which was interpreted as 2015; accepted article preview online 21 May 2015 an increased alcohol ‘wanting’ (Vengeliene et al, 2013). The Relapse to alcohol use is controlled by melatonin V Vengeliene et al 2898 change in the temporal distribution of the alcohol consump- (generously provided by Abbvie, Ludwigshafen, Germany) tion is associated with the loss of normal diurnal behavior, was suspended in 1% hydroxypropyl methylcellulose (Sigma- which may possibly be interpreted as development of Aldrich, Taufkirchen, Germany) and injected as a volume of compulsive alcohol drinking and addictive behavior. It 1 ml/kg IP. SB242084 (generously provided by Abbvie, should be noted that although the ADE provides a suitable Ludwigshafen, Germany) was dissolved in water for injec- model to study the impact of alcohol re-exposure on relapse- tions (aqua ad iniectabilia, Braun, Melsungen AG, Germany) like behavior (Lê and Shaham, 2002), it mimics only some and injected as a volume of 1 ml/kg IP. Control animals aspects of human relapse. Transitory nature of the elevated received an equal volume of respective vehicle. post-abstinence alcohol consumption in rats is one char- acteristic that distinguish relapse drinking in rats from that Drinkometer System seen in human alcoholics. Nevertheless, clinically effective antirelapse drugs acamprosate and naltrexone were shown to The drinkometer system has been developed together with TSE effectively reduce the ADE in rats demonstrating predictive Systems (Bad Homburg, Germany). It enables continuous value of this animal model (Spanagel, 2009). In recent years, long-term monitoring of liquid consumption by amount and the ADE animal model has become widely used for time in a standard rat home cage (Eurostandard Type III). examining the efficacy of pharmacological agents in The system is equipped with four drinking stations to preventing compulsive alcohol consumption and relapse allow liquid choice. The drinking station consists of a glass (Vengeliene et al, 2008; 2014). vessel containing the liquid and a high-precision sensor for In order to assess the role of the melatonin system in weighing the amount of liquid removed from the glass vessel. alcohol relapse we studied the effects of agomelatine, a potent Spillage and evaporation are minimized by using special bottle MT1 and MT2 agonist, which also displays antagonistic caps. Monitoring of all drinking stations is carried out by a — activity on 5-HT2C receptors. The affinity of this drug for computer. The system features ultrahigh resolution down to other 5-HT receptors is low (Millan et al, 2003). Two further 0.01 g. The whole system is mounted to a custom-made free- drug treatments were included in our study to clarify the swinging steel frame in order to avoid any environmental contribution of MT1/MT2 receptors and 5-HT2C receptors in disturbances. The drinkometer system measures the weight of mediating the effects of agomelatine on relapse-like drinking a vessel in 200 ms steps and saves it in 1-s steps. The normal and its action on circadian rhythm. For this purpose a high sampling can be set with minimum 1 min intervals. For the dose of melatonin was administered repeatedly either at the present study, sampling was performed at 5 min intervals. end or at the onset of the light phase. We also tested the effect of 5-HT2C antagonist SB242084. Both agomelatine and Long-Term Ethanol Consumption with Repeated SB242084 were administered at the end of the light phase. To Deprivation Phases characterize temporal characteristics of drinking behavior we registered drinking patterns with a high temporal resolution After 2 weeks of habituation to the animal room, rats were using a drinkometer system (Vengeliene et al, 2013). given ad libitum access to tap water and 5, 10, and 20% ethanol solutions (v/v). The first 2-week deprivation period was introduced after 8 weeks of continuous ethanol MATERIALS AND METHODS availability. After this deprivation period, rats were given Animals access to ethanol again. This access was further interrupted repeatedly with deprivation periods in a random manner (ie, Fifty-six 2-month-old male Wistar rats (from our own the duration of following drinking and deprivation phases breeding colony at the CIMH, Mannheim, Germany) were was irregular: approximately 4–6 and 2–3 weeks, respec- used. All animals were housed individually in standard rat tively). The long-term
Load more

Recommended publications
  • Drugs Inducing Insomnia As an Adverse Effect
    2 Drugs Inducing Insomnia as an Adverse Effect Ntambwe Malangu University of Limpopo, Medunsa Campus, School of Public Health, South Africa 1. Introduction Insomnia is a symptom, not a stand-alone disease. By definition, insomnia is "difficulty initiating or maintaining sleep, or both" or the perception of poor quality sleep (APA, 1994). As an adverse effect of medicines, it has been documented for several drugs. This chapter describes some drugs whose safety profile includes insomnia. In doing so, it discusses the mechanisms through which drug-induced insomnia occurs, the risk factors associated with its occurrence, and ends with some guidance on strategies to prevent and manage drug- induced insomnia. 2. How drugs induce insomnia There are several mechanisms involved in the induction of insomnia by drugs. Some drugs affects sleep negatively when being used, while others affect sleep and lead to insomnia when they are withdrawn. Drugs belonging to the first category include anticonvulsants, some antidepressants, steroids and central nervous stimulant drugs such amphetamine and caffeine. With regard to caffeine, the mechanism by which caffeine is able to promote wakefulness and insomnia has not been fully elucidated (Lieberman, 1992). However, it seems that, at the levels reached during normal consumption, caffeine exerts its action through antagonism of central adenosine receptors; thereby, it reduces physiologic sleepiness and enhances vigilance (Benington et al., 1993; Walsh et al., 1990; Rosenthal et al., 1991; Bonnet and Arand, 1994; Lorist et al., 1994). In contrast to caffeine, methamphetamine and methylphenidate produce wakefulness by increasing dopaminergic and noradrenergic neurotransmission (Gillman and Goodman, 1985). With regard to withdrawal, it may occur in 40% to 100% of patients treated chronically with benzodiazepines, and can persist for days or weeks following discontinuation.
    [Show full text]
  • Sleep Inducing Toothpaste Made with Natural Herbs and a Natural Hormone
    Sleep inducing toothpaste made with natural herbs and a natural hormone Abstract A toothpaste composition for inducing sleep while simultaneously promoting intraoral cleanliness, which includes toothpaste base ingredients and at least one sleep- inducing natural herb or hormone. The sleep-inducing natural herbs and hormone are selected from the group consisting of Chamomile, Lemon Balm, Passion Flower, and Valerian, and the hormone Melatonin. The sleep-inducing natural herbs are in a range of 0.25% to 18% by weight of the composition. Description of the Invention FIELD OF THE INVENTION The following natural herbs and natural hormone in combination with toothpaste is used at night to improve sleep. The expected dose of toothpaste is calculated at 2 grams. The ingredients have been assessed for range of daily dose for best effects, toxicity in normal range, recommended proportion of each, and water solubility of key constituents. BACKGROUND OF THE INVENTION It is an object of the present invention to provide a sleep-inducing toothpaste or mouth spray which includes sleep-inducing natural herbs and a natural hormone. It is a further object of the present invention to provide a sleep-inducing toothpaste which includes toothpaste base ingredients and natural herbs being Chamomile, Lemon Balm, Passion Flower, Valerian and the natural hormone Melatonin. SUMMARY OF THE INVENTION A toothpaste composition is provided for inducing sleep while simultaneously promoting intraoral cleanliness, which includes toothpaste base ingredients and at least one sleep-inducing natural herb or hormone. The sleep-inducing natural herbs and hormone are selected from the group consisting of the natural herbs Chamomile, Lemon Balm, Passion Flower, and Valerian, and the natural hormone Melatonin.
    [Show full text]
  • The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease
    brain sciences Perspective The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease Jung Goo Lee 1,2 , Young Sup Woo 3, Sung Woo Park 2,4, Dae-Hyun Seog 5, Mi Kyoung Seo 6 and Won-Myong Bahk 3,* 1 Department of Psychiatry, College of Medicine, Haeundae Paik Hospital, Inje University, Busan 47392, Korea; [email protected] 2 Paik Institute for Clinical Research, Department of Health Science and Technology, Graduate School, Inje University, Busan 47392, Korea; [email protected] 3 Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea; [email protected] 4 Department of Convergence Biomedical Science, College of Medicine, Inje University, Busan 47392, Korea 5 Department of Biochemistry, College of Medicine, Inje University, Busan 47392, Korea; [email protected] 6 Paik Institute for Clinical Research, Inje University, Busan 47392, Korea; [email protected] * Correspondence: [email protected] Received: 16 September 2019; Accepted: 19 October 2019; Published: 21 October 2019 Abstract: Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and effects of melatonin. In recent studies, melatonin was shown to have antioxidant activity and, possibly, to affect the development of Alzheimer’s disease (AD). In addition, melatonin has neuroprotective effects and affects neuroplasticity, thus indicating potential antidepressant properties. In the present review, the new functions of melatonin are summarized and a therapeutic target for the development of new drugs based on the mechanism of action of melatonin is proposed.
    [Show full text]
  • THE USE of MIRTAZAPINE AS a HYPNOTIC O Uso Da Mirtazapina Como Hipnótico Francisca Magalhães Scoralicka, Einstein Francisco Camargosa, Otávio Toledo Nóbregaa
    ARTIGO ESPECIAL THE USE OF MIRTAZAPINE AS A HYPNOTIC O uso da mirtazapina como hipnótico Francisca Magalhães Scoralicka, Einstein Francisco Camargosa, Otávio Toledo Nóbregaa Prescription of approved hypnotics for insomnia decreased by more than 50%, whereas of antidepressive agents outstripped that of hypnotics. However, there is little data on their efficacy to treat insomnia, and many of these medications may be associated with known side effects. Antidepressants are associated with various effects on sleep patterns, depending on the intrinsic pharmacological properties of the active agent, such as degree of inhibition of serotonin or noradrenaline reuptake, effects on 5-HT1A and 5-HT2 receptors, action(s) at alpha-adrenoceptors, and/or histamine H1 sites. Mirtazapine is a noradrenergic and specific serotonergic antidepressive agent that acts by antagonizing alpha-2 adrenergic receptors and blocking 5-HT2 and 5-HT3 receptors. It has high affinity for histamine H1 receptors, low affinity for dopaminergic receptors, and lacks anticholinergic activity. In spite of these potential beneficial effects of mirtazapine on sleep, no placebo-controlled randomized clinical trials of ABSTRACT mirtazapine in primary insomniacs have been conducted. Mirtazapine was associated with improvements in sleep on normal sleepers and depressed patients. The most common side effects of mirtazapine, i.e. dry mouth, drowsiness, increased appetite and increased body weight, were mostly mild and transient. Considering its use in elderly people, this paper provides a revision about studies regarding mirtazapine for sleep disorders. KEYWORDS: sleep; antidepressive agents; sleep disorders; treatment� A prescrição de hipnóticos aprovados para insônia diminuiu em mais de 50%, enquanto de antidepressivos ultrapassou a dos primeiros.
    [Show full text]
  • Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway
    Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway Hongjie Zhu1., Mikhail B. Bogdanov2., Stephen H. Boyle1, Wayne Matson3, Swati Sharma3, Samantha Matson3,4, Erik Churchill1, Oliver Fiehn5, John A. Rush6, Ranga R. Krishnan1,6, Eve Pickering7, Marielle Delnomdedieu8, Rima Kaddurah-Daouk1*, Pharmacometabolomics Research Network 1 Department of Psychiatry and Behavioral Sciences, Duke University, Durham, North Carolina, United States of America, 2 Department of Neurology and Neuroscience Weill Cornell Medical College, New York, New York, United States of America, 3 Department of Systems Biochemistry, Bedford VA Medical Center, Bedford, Massachusetts, United States of America, 4 Massachusetts General Hospital, Boston, Massachusetts, United States of America, 5 Genome Center, University of California Davis, Davis, California, United States of America, 6 Duke-NUS Graduate Medical School, Singapore, Singapore, 7 Pfizer Global R&D, Clinical Research Statistics, Groton, Connecticut, United States of America, 8 Pfizer Global R&D, Neuroscience Clinical Research, Groton, Connecticut, United States of America Abstract Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17).
    [Show full text]
  • Melatonin Protects Against the Effects of Chronic Stress on Sexual Behaviour in Male Rats
    MOTIVATION, EMOTION, FEEDING, DRINKING NEUROREPORT Melatonin protects against the effects of chronic stress on sexual behaviour in male rats Lori A. Brotto, Boris B. GorzalkaCA and Amanda K. LaMarre Department of Psychology, 2136 West Mall, Vancouver, BC, Canada V6T 1Z4 CACorresponding Author Received 9 July 2001; accepted 24 August 2001 The effects of chronic mild stress (CMS) on both sexual but not the effects on either spontaneous WDS or WDS in behaviour and wet dog shakes (WDS), a serotonergic type 2A response to the 5-HT2A agonist 1-(2,5-dimethoxy-4-iodophe- (5-HT2A) receptor-mediated behaviour, were explored in the nyl)-2-aminopropane, suggesting a mechanism of action other male rat. In addition, the possible attenuation of these effects than exclusive 5-HT2A antagonism. These results are the ®rst by chronic treatment with melatonin, a putative 5-HT2A to demonstrate that melatonin signi®cantly protects against the antagonist, was examined. The CMS procedure resulted in a detrimental effects of a chronic stressor on sexual behaviour. signi®cant increase in WDS and an overall decrease in all NeuroReport 12:3465±3469 & 2001 Lippincott Williams & aspects of sexual behaviour. Concurrent melatonin administra- Wilkins. tion attenuated the CMS-induced effects on sexual behaviour, Key words: Chronic mild stress; 5-HT2A receptors; Melatonin; Serotonin; Sexual behaviour INTRODUCTION vioural effect of melatonin is mediated via a reduction in The chronic mild stress (CMS) procedure, in which rats are 5-HT2A receptor activity rather than altered central 5-HT2A repeatedly exposed to a variety of mild stressors, is receptor density [8]. The demonstration that melatonin associated with behavioural and biochemical sequelae that reduces the concentration-dependent 5-HT2A receptor- are commonly associated with anhedonia [1].
    [Show full text]
  • Drug Repurposing for the Management of Depression: Where Do We Stand Currently?
    life Review Drug Repurposing for the Management of Depression: Where Do We Stand Currently? Hosna Mohammad Sadeghi 1,†, Ida Adeli 1,† , Taraneh Mousavi 1,2, Marzieh Daniali 1,2, Shekoufeh Nikfar 3,4,5 and Mohammad Abdollahi 1,2,* 1 Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran; [email protected] (H.M.S.); [email protected] (I.A.); [email protected] (T.M.); [email protected] (M.D.) 2 Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran 3 Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran 1417614411, Iran; [email protected] 4 Pharmaceutical Sciences Research Center (PSRC) and the Pharmaceutical Management and Economics Research Center (PMERC), Evidence-Based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran 1417614411, Iran 5 Department of Pharmacoeconomics and Pharmaceutical Administration, School of Pharmacy, Tehran University of Medical Sciences, Tehran 1417614411, Iran * Correspondence: [email protected] † Equally contributed as first authors. Citation: Mohammad Sadeghi, H.; Abstract: A slow rate of new drug discovery and higher costs of new drug development attracted Adeli, I.; Mousavi, T.; Daniali, M.; the attention of scientists and physicians for the repurposing and repositioning of old medications. Nikfar, S.; Abdollahi, M. Drug Experimental studies and off-label use of drugs have helped drive data for further studies of ap- Repurposing for the Management of proving these medications.
    [Show full text]
  • Us 2008/0280991 A1 8, 2007. Pdco
    US 20080280991A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0280991 A1 Gant et al. (43) Pub. Date: Nov. 13, 2008 (54) SUBSTITUTED NAPHTHALENES (52) U.S. Cl. ......................................... 514/630; 564/219 (75) Inventors: Thomas G. Gant, Carlsbad, CA (US); Sepehr Sarshar, Cardiff by the Sea, CA (US) (57) ABSTRACT Correspondence Address: Disclosed herein are substituted naphthalene-based melato GLOBAL PATENT GROUP - APX nin (MT) receptor modulators and/or 5-HT receptor modula Ms. LaVern Hall tors of Formula I, process of preparation thereof, pharmaceu 10411 Clayton Road, Suite 304 tical compositions thereof, and methods of use thereof. ST. LOUIS, MO 63131 (US) (73) Assignee: AUSPEX O Formula I PHARMACEUTICALS, INC., Vista, CA (US) Ran R15 (21) Appl. No.: 12/116,636 R R16 R11 R13 7 (22) Filed: May 7, 2008 R12 R16 Related U.S. Application Data Ro (60) Provisional application No. 60/928,343, filed on May R O Rs 2 R3 8, 2007. Publication Classification PDCOR R (51) Int. Cl. Rs R6 A6 IK3I/I65 (2006.01) C07C 23.3/05 (2006.01) US 2008/0280991 A1 Nov. 13, 2008 SUBSTITUTED NAPHTHALENES nant metabolite is a naphthol. “S 21517. that has 100-fold less potency for the melatonin receptor than the parent com pound. Long term toxicology studies of these metabolites are 0001. This application claims the benefit of priority of lacking. All of these transformations, among other potential U.S. provisional application No. 60/928,343, filed May 8, transformations, can and do occur through polymorphically 2007, the disclosure of which is hereby incorporated by ref expressed enzymes thus exacerbating interpatient variability.
    [Show full text]
  • Npp200972.Pdf
    Neuropsychopharmacology (2009) 34, 2390–2403 & 2009 Nature Publishing Group All rights reserved 0893-133X/09 $32.00 www.neuropsychopharmacology.org Mechanisms Contributing to the Phase-Dependent Regulation of Neurogenesis by the Novel Antidepressant, Agomelatine, in the Adult Rat Hippocampus Ame´lie Soumier1, Mounira Banasr1, Sylviane Lortet1, Fre´de´rique Masmejean1, Nathalie Bernard1, Lydia Kerkerian-Le-Goff1, Cecilia Gabriel2, Mark J Millan3, Elisabeth Mocaer2 and Annie Daszuta*,1 1 2 3 IC2N, IBDML, UMR 6216, Marseille, France; IRIS, Courbevoie, France; IDR Servier, Croissy-sur-Seine, France Agomelatine is a novel antidepressant acting as a melatonergic receptor agonist and serotonergic (5-HT ) receptor antagonist. In adult 2C rats, chronic agomelatine treatment enhanced cell proliferation and neurogenesis in the ventral hippocampus (VH), a region pertinent to mood disorders. This study compared the effects of agomelatine on cell proliferation, maturation, and survival and investigated the cellular mechanisms underlying these effects. Agomelatine increased the ratio of mature vs immature neurons and enhanced neurite outgrowth of granular cells, suggesting an acceleration of maturation. The influence of agomelatine on maturation and survival was accompanied by a selective increase in the levels of BDNF (brain-derived neurotrophic factor) vs those of VEGF (vascular endothelial factor) and IGF-1 (insulin-like growth factor 1), which were not affected. Agomelatine also activated several cellular signals (extracellular signal-regulated kinase1/2, protein kinase B, and glycogen synthase kinase 3b) known to be modulated by antidepressants and implicated in the control of proliferation/survival. Furthermore, as agomelatine possesses both melatonergic agonist and serotonergic (5-HT2C) antagonist properties, we determined whether melatonin and 5-HT2C receptor antagonists similarly influence cell proliferation and survival.
    [Show full text]
  • Insomnia Disorder a VA Clinician’S Guide to Managing Insomnia Disorder (2019) Contents Insomnia Disorder
    Insomnia Disorder A VA Clinician’s Guide to Managing Insomnia Disorder (2019) Contents Insomnia Disorder .................................................................................................... 3 Risks in elderly patients and patients with dementia .................................15 Background ................................................................................................................ 3 Provider perceptions vs reality ............................................................................16 Figure 1. Stepped Care for Management of Insomnia Disorder .............. 3 Figure 5. Weighing the potential risks versus benefits of Table 1. Brief summary of the ISI ......................................................................... 4 medication use .........................................................................................................16 Figure 2. Acute Insomnia to Insomnia Disorder ............................................ 5 Doxepin ........................................................................................................................17 Clinical Pearl ............................................................................................................... 5 Figure 6. Doxepin Use .............................................................................................18 Figure 3. Common causes of sleep disturbance ........................................... 6 Ramelteon ...................................................................................................................18
    [Show full text]
  • Herbal Remedies and Sleep
    HERBAL REMEDIES AND SLEEP • Some people use herbal remedies to treat sleep problems. They may choose this in preference to sleeping pills. • There have been studies on some of these herbs. However, not all of them have been conducted properly. For some herbs, there is virtually no evidence to show whether they are effective or not. • The most frequently studied herbs are Valerian, Kava, Hops, Chamomile, and Passionflower. However, there is little convincing evidence to suggest that they work well for improving sleep. • Some herbal remedies have been associated with adverse health effects. Note: All words that are underlined relate to topics in the Sleep Health Foundation Information Library at www.sleephealthfoundation.org.au 1. Why try herbs to help your sold by a specific manufacturer for a certain time-period. Trials testing effectiveness are expensive, and without a patent, companies may not sleep? be able to recover their costs through guaranteed sales, even if the herb has potential. However, there have been studies of some herbs About 40% of people use alternative or complementary medicines at used for insomnia and anxiety. Here we focus on herbs where least occasionally, and 4.5% use them to treat sleep problem. Some reasonable information exists from clinical research trials. people who are concerned about using sleeping pills will turn to herbal remedies to help them sleep (see our page on Sleeping Tablets). Melatonin is not a herbal remedy (for more information see Melatonin). 3. What does the evidence say about herbs helping sleep? 2. Has the effectiveness of herbs In the table below, we look at the effectiveness of eight herbal remedies in treating sleep problems as treatments of insomnia.
    [Show full text]
  • Association of Selective Serotonin Reuptake Inhibitors with the Risk for Spontaneous Intracranial Hemorrhage
    Supplementary Online Content Renoux C, Vahey S, Dell’Aniello S, Boivin J-F. Association of selective serotonin reuptake inhibitors with the risk for spontaneous intracranial hemorrhage. JAMA Neurol. Published online December 5, 2016. doi:10.1001/jamaneurol.2016.4529 eMethods 1. List of Antidepressants for Cohort Entry eMethods 2. List of Antidepressants According to the Degree of Serotonin Reuptake Inhibition eMethods 3. Potential Confounding Variables Included in Multivariate Models eMethods 4. Sensitivity Analyses eFigure. Flowchart of Incident Antidepressant (AD) Cohort Definition and Case- Control Selection eTable 1. Crude and Adjusted Rate Ratios of Intracerebral Hemorrhage Associated With Current Use of SSRIs Relative to TCAs eTable 2. Crude and Adjusted Rate Ratios of Subarachnoid Hemorrhage Associated With Current Use of SSRIs Relative to TCAs eTable 3. Crude and Adjusted Rate Ratios of Intracranial Extracerebral Hemorrhage Associated With Current Use of SSRIs Relative to TCAs. eTable 4. Crude and Adjusted Rate Ratios of Intracerebral Hemorrhage Associated With Current Use of Antidepressants With Strong Degree of Inhibition of Serotonin Reuptake Relative to Weak eTable 5. Crude and Adjusted Rate Ratios of Subarachnoid Hemorrhage Associated With Current Use of Antidepressants With Strong Degree of Inhibition of Serotonin Reuptake Relative to Weak eTable 6. Crude and Adjusted Rate Ratios of Intracranial Extracerebral Hemorrhage Associated With Current Use of Antidepressants With Strong Degree of Inhibition of Serotonin Reuptake Relative to Weak This supplementary material has been provided by the authors to give readers additional information about their work. © 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 eMethods 1.
    [Show full text]