Nocturnal hyperactivity, increased social novelty preference and delayed extinction of fear responses in post-weaning socially isolated mice

Naert, Arne; Callaerts-Végh, Zsuzsanna; D’Hooge, Rudi

doi:10.1016/j.brainresbull.2011.03.027

Cited by 52 publications

(41 citation statements)

References 47 publications

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“…Importantly, a recent rodent study identified a link between chronic ethanol exposure and later PTSD-like impairments in extinction learning (Holmes et al, 2012). A similar effect has also been observed in mice exposed to adolescent isolation; these animals did eventually acquire extinction learning, but at a markedly slower rate than group housed conspecifics (Naert et al, 2011). Hence, disrupted (or at least delayed) acquisition of extinction learning may be an additional behavioral change associated with adolescent isolation in an animal model of voluntary anxiety-related ethanol intake.…”

Section: Discussionsupporting

confidence: 64%

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

et al. 2015

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Alcohol use disorder, anxiety disorders, and post-traumatic stress disorder (PTSD) are highly comorbid, and exposure to chronic stress during adolescence may increase the incidence of these conditions in adulthood. Efforts to identify the common stress-related mechanisms driving these disorders have been hampered, in part, by a lack of reliable preclinical models that replicate their comorbid symptomatology. Prior work by us, and others, has shown that adolescent social isolation increases anxiety-like behaviors and voluntary ethanol consumption in adult male Long-Evans rats. Here we examined whether social isolation also produces deficiencies in extinction of conditioned fear, a hallmark symptom of PTSD. Additionally, as disrupted noradrenergic signaling may contribute to alcoholism, we examined the effect of anxiolytic medications that target noradrenergic signaling on ethanol intake following adolescent social isolation. Our results confirm and extend previous findings that adolescent social isolation increases anxiety-like behavior and enhances ethanol intake and preference in adulthood. Additionally, social isolation is associated with a significant deficit in the extinction of conditioned fear and a marked increase in the ability of noradrenergic therapeutics to decrease ethanol intake. These results suggest that adolescent social isolation not only leads to persistent increases in anxiety-like behaviors and ethanol consumption, but also disrupts fear extinction, and as such may be a useful preclinical model of stress-related psychopathology. Our data also suggest that disrupted noradrenergic signaling may contribute to escalated ethanol drinking following social isolation, thus further highlighting the potential utility of noradrenergic therapeutics in treating the deleterious behavioral sequelae associated with early life stress.

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Section: Discussionsupporting

confidence: 64%

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

et al. 2015

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“…In socially isolated wild type mice we observed a reduced exploration behavior in an open field compared to unstressed mice, resembling previous observations in rats (Avital et al, 2006). However, studies in mice rather report hyperactivity (Pietropaolo et al, 2008a,b) or no changes compared to group-housed animals (Varty et al, 2006; Naert et al, 2011). Moreover, an enhanced exploration of open arms occurred in the elevated plus maze in our experiments, which may reflect an increased arousal response as previously been observed in chronically stressed C57BL/6 mice (Mozhui et al, 2010) and stress-sensitive mutant mice (Stork et al, 2000b).…”

Section: Discussionmentioning

confidence: 99%

GAD65 haplodeficiency conveys resilience in animal models of stress-induced psychopathology

Müller

Obata

Richter‐Levin

et al. 2014

Front. Behav. Neurosci.

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GABAergic mechanisms are critically involved in the control of fear and anxiety, but their role in the development of stress-induced psychopathologies, including post-traumatic stress disorder (PTSD) and mood disorders is not sufficiently understood. We studied these functions in two established mouse models of risk factors for stress-induced psychopathologies employing variable juvenile stress and/or social isolation. A battery of emotional tests in adulthood revealed the induction of contextually generalized fear, anxiety, hyperarousal and depression-like symptoms in these paradigms. These reflect the multitude and complexity of stress effects in human PTSD patients. With factor analysis we were able to identify parameters that reflect these different behavioral domains in stressed animals and thus provide a basis for an integrated scoring of affectedness more closely resembling the clinical situation than isolated parameters. To test the applicability of these models to genetic approaches we further tested the role of GABA using heterozygous mice with targeted mutation of the GABA synthesizing enzyme GAD65 [GAD65(+/−) mice], which show a delayed postnatal increase in tissue GABA content in limbic and cortical brain areas. Unexpectedly, GAD65(+/−) mice did not show changes in exploratory activity regardless of the stressor type and were after the variable juvenile stress procedure protected from the development of contextual generalization in an auditory fear conditioning experiment. Our data demonstrate the complex nature of behavioral alterations in rodent models of stress-related psychopathologies and suggest that GAD65 haplodeficiency, likely through its effect on the postnatal maturation of GABAergic transmission, conveys resilience to some of these stress-induced effects.

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“…A simplified version of the social novelty preference protocol (Naert et al, 2011) was adopted. The setup consisted of a 40 Â 40 Â 40 cm melamine arena (black floor and grey walls), containing two inverted wire cages (inverted cups, diameter 12 cm, height 15.5 cm) placed diagonally in opposite corners of the arena.…”

Section: Social Preferencementioning

confidence: 99%

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice

Pilz

Trojan

Quiles

et al. 2014

Chronobiology International

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Circadian rhythm disturbances are among the risk factors for depression, but specific animal models are lacking. This study aimed to characterize the effects of acute rhythm disruption in mice and investigate the effects of imipramine and N-acetylcysteine (NAC) on rhythm disruption-induced changes. Mice were exposed to 12:12-hour followed by 10:10-hour light:dark cycles (LD); under the latter, mice were treated with saline, imipramine or NAC. Rhythms of rest/activity and temperature were assessed with actigraphs and iButtons, respectively. Hole-board and social preference tests were performed at the beginning of the experiment and again at the 8th 10:10 LD, when plasma corticosterone and IL-6 levels were also assessed. Actograms showed that the 10:10 LD schedule prevents the entrainment of temperature and activity rhythms for at least 13 cycles. Subsequent light regimen change activity and temperature amplitudes showed similar patterns of decline followed by recovery attempts. During the 10:10 LD schedule, activity and temperature amplitudes were significantly decreased (paired t test), an effect exacerbated by imipramine (ANOVA/SNK). The 10:10 LD schedule increased anxiety (paired t test), an effect prevented by NAC (30 mg/kg). This study identified mild but significant behavioral changes at specific time points after light regimen change. We suggest that if repeated overtime, these subtle changes may contribute to lasting behavioral disturbancess relevant to anxiety and mood disorders. Data suggest that imipramine may contribute to sustained rhythm disturbances, while NAC appears to prevent rhythm disruption-induced anxiety. Associations between sleep/circadian disturbances and the recurrence of depressive episodes underscore the relevance of potential drug-induced maintenance of disturbed rhythms.

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Nocturnal hyperactivity, increased social novelty preference and delayed extinction of fear responses in post-weaning socially isolated mice

Cited by 52 publications

References 47 publications

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling

GAD65 haplodeficiency conveys resilience in animal models of stress-induced psychopathology

Effects of N-acetylcysteine and imipramine in a model of acute rhythm disruption in BALB/c mice

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