The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats

Kołtunowska, Dorota; Gibuła-Bruzda, Ewa; Kotlińska, Jolanta

doi:10.1016/j.pnpbp.2013.04.013

Cited by 26 publications

(24 citation statements)

References 74 publications

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“…The increased expression of mGlu1, mGlu5, and GluN2b expression in the AcbSh of adult bingers paralleled the hyper-anxious behaviors displayed by adult bingers in the marble burying test and FST. Given the well-established role of glutamate in anxiety (Bergink et al, 2004; Swanson et al, 2005; Simon and Gorman, 2006; Kotlinska and Bochenski, 2008; Koltunowska et al, 2013), these results were consistent with our hypothesis that withdrawal-induced anxiety would be associated with increased protein indices of glutamatergic transmission within the AcbSh, thereby further implicating AcbSh excitability in withdrawal-induced negative affect. The AcbSh also receives significant glutamatergic innervation from the amygdala, which is highly susceptible to alcohol-induced perturbation and is known to mediate many aspects of withdrawal-induced negative affect (Christian et al, 2012; Gilpin et al, 2015).…”

Section: Discussionsupporting

confidence: 89%

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

Lee

Coelho

McGregor

et al. 2016

Front. Cell. Neurosci.

124

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Binge-drinking is the most prevalent form of alcohol abuse and while an early life history of binge-drinking is a significant risk factor for subsequent alcoholism and co-morbid affective disorders, relatively little is known regarding the biobehavioral impact of binge-drinking during the sensitive neurodevelopmental period of adolescence. In adult mice, a month-long history of binge-drinking elicits a hyper-glutamatergic state within the nucleus accumbens (Acb), coinciding with hyper-anxiety. Herein, we employed a murine model of binge-drinking to determine whether or not: (1) withdrawal-induced changes in brain and behavior differ between adult and adolescent bingers; and (2) increased behavioral signs of negative affect and changes in Acb expression of glutamate-related proteins would be apparent in adult mice with less chronic binge-drinking experience (14 days, approximating the duration of mouse adolescence). Adult and adolescent male C57BL/6J mice were subjected to a 14-day binge-drinking protocol (5, 10, 20 and 40% alcohol (v/v) for 2 h/day), while age-matched controls received water. At 24 h withdrawal, half of the animals from each group were assayed for negative affect, while tissue was sampled from the shell (AcbSh) and core (AcbC) subregions of the remaining mice for immunoblotting analyses. Adult bingers exhibited hyper-anxiety when tested for defensive marble burying. Additionally, adult bingers showed increased mGlu1, mGlu5, and GluN2b expression in the AcbSh and PKCε and CAMKII in the AcbC. Compared to adults, adolescent mice exhibited higher alcohol intake and blood alcohol concentrations (BACs); however, adolescent bingers did not show increased anxiety in the marble-burying test. Furthermore, adolescent bingers also failed to exhibit the same alcohol-induced changes in mGlu and kinase protein expression seen in the adult bingers. Irrespective of age, bingers exhibited behavioral hyperactivity in the forced swim test (FST) compared to water drinkers, which was paralleled by an increase in AcbC levels of GluN2b. Thus, a 2-week period of binge-drinking is sufficient to produce a hyper-anxious state and related increases in protein indices of Acb glutamate function. In contrast, adolescents were resilient to many of the effects of early alcohol withdrawal and this attenuated sensitivity to the negative consequences of binge drinking may facilitate greater alcohol intake in adolescent drinkers.

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Section: Discussionsupporting

confidence: 89%

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

Lee

Coelho

McGregor

et al. 2016

Front. Cell. Neurosci.

124

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“…Memantine pretreatment fully blocked compulsive eating, bringing the intake of the Palatable food group to the control Chow level. We can confidently exclude that the effect of drug treatment on the light/dark conflict test was influenced by a potential anxiogenic effect, as memantine has been shown to exert either no effect or anxiolytic effects (Koltunowska et al, 2013;Minkeviciene et al, 2008).…”

Section: Discussionmentioning

confidence: 98%

The Uncompetitive N-methyl-D-Aspartate Antagonist Memantine Reduces Binge-Like Eating, Food-Seeking Behavior, and Compulsive Eating: Role of the Nucleus Accumbens Shell

Smith

Rao

Velázquez-Sánchez

et al. 2014

Neuropsychopharmacol

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Binge-eating disorder is characterized by excessive, uncontrollable consumption of palatable food within brief periods of time. The role of the glutamatergic N-methyl-D-aspartate (NMDA) receptor system in hedonic feeding is poorly understood. The aim of this study was to characterize the effects of the uncompetitive NMDA receptor antagonist memantine on palatable food-induced behavioral adaptations using a rat model, which mimics the characteristic symptomatology observed in binge-eating disorder. For this purpose, we allowed male Wistar rats to respond to obtain a highly palatable, sugary diet (Palatable group) or a regular chow diet (Chow control group), for 1 h a day, under a fixed-ratio 1 (FR1) schedule of reinforcement. Upon stabilization of food responding, we tested the effects of memantine on the Chow and Palatable food groups' intake. Then, we tested the effects of memantine on food-seeking behavior, under a second-order schedule of reinforcement. Furthermore, we investigated the effects of memantine on the intake of food when it was offered in an aversive, bright compartment of a light/dark conflict test. Finally, we evaluated the effects of memantine on FR1 responding for food, when microinfused into the nucleus accumbens (NAcc) shell or core. Memantine dose-dependently decreased binge-like eating and fully blocked food-seeking behavior and compulsive eating, selectively in the Palatable food group. The drug treatment did not affect performance of the control Chow food group. Finally, intra-NAcc shell, but not core, microinfusion of memantine decreased binge-like eating. Together, these findings substantiate a role of memantine as a potential pharmacological treatment for binge-eating disorder.

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“…In an amphetamine withdrawal-evoked anxiety rodent model, acamprosate treatment increased time in open in the elevated plus maze without a change in locomotor behavior. Another group found that acamprosate reduced social anxiety in a combination stress/ethanol withdrawal rodent model, further supporting the drug’s utility at alleviating anxiety in a manner pertinent to humans with FXS [112, 113]. Koltunowska et al suggested that this anxiolytic effect of acamprosate may be due to its effects at mGluR receptors which is thought to be a key player in FXS pathophysiology [6].…”

Section: Discussionmentioning

confidence: 99%

Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety

Schaefer

Davenport

Grainger

et al. 2017

J Neurodevelop Disord

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BackgroundFragile X Syndrome (FXS) occurs as a result of a silenced fragile X mental retardation 1 gene (FMR1) and subsequent loss of fragile X mental retardation protein (FMRP) expression. Loss of FMRP alters excitatory/inhibitory signaling balance, leading to increased neuronal hyperexcitability and altered behavior. Acamprosate (the calcium salt of N-acetylhomotaurinate), a drug FDA-approved for relapse prevention in the treatment of alcohol dependence in adults, is a novel agent with multiple mechanisms that may be beneficial for people with FXS. There are questions regarding the neuroactive effects of acamprosate and the significance of the molecule’s calcium moiety. Therefore, the electrophysiological, cellular, molecular, and behavioral effects of acamprosate were assessed in the Fmr1 -/y (knock out; KO) mouse model of FXS controlling for the calcium salt in several experiments.Methods Fmr1 KO mice and their wild-type (WT) littermates were utilized to assess acamprosate treatment on cortical UP state parameters, dendritic spine density, and seizure susceptibility. Brain extracellular-signal regulated kinase 1/2 (ERK1/2) activation was used to investigate this signaling molecule as a potential biomarker for treatment response. Additional adult mice were used to assess chronic acamprosate treatment and any potential effects of the calcium moiety using CaCl2 treatment on behavior and nuclear ERK1/2 activation.ResultsAcamprosate attenuated prolonged cortical UP state duration, decreased elevated ERK1/2 activation in brain tissue, and reduced nuclear ERK1/2 activation in the dentate gyrus in KO mice. Acamprosate treatment modified behavior in anxiety and locomotor tests in Fmr1 KO mice in which control-treated KO mice were shown to deviate from control-treated WT mice. Mice treated with CaCl2 were not different from saline-treated mice in the adult behavior battery or nuclear ERK1/2 activation.ConclusionsThese data indicate that acamprosate, and not calcium, improves function reminiscent of reduced anxiety-like behavior and hyperactivity in Fmr1 KO mice and that acamprosate attenuates select electrophysiological and molecular dysregulation that may play a role in the pathophysiology of FXS. Differences between control-treated KO and WT mice were not evident in a recognition memory test or in examination of acoustic startle response/prepulse inhibition which impeded conclusions from being made about the treatment effects of acamprosate in these instances.Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-017-9184-y) contains supplementary material, which is available to authorized users.

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The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats

Cited by 26 publications

References 74 publications

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

Adolescent Mice Are Resilient to Alcohol Withdrawal-Induced Anxiety and Changes in Indices of Glutamate Function within the Nucleus Accumbens

The Uncompetitive N-methyl-D-Aspartate Antagonist Memantine Reduces Binge-Like Eating, Food-Seeking Behavior, and Compulsive Eating: Role of the Nucleus Accumbens Shell

Acamprosate in a mouse model of fragile X syndrome: modulation of spontaneous cortical activity, ERK1/2 activation, locomotor behavior, and anxiety

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