Running‐induced anxiety is dependent on increases in hippocampal neurogenesis

Onksen, Jennifer; Briand, Lisa A.; Galante, Raymond J.; Pack, Allan I.; Blendy, Julie A.

doi:10.1111/j.1601-183x.2012.00788.x

Cited by 25 publications

(26 citation statements)

References 51 publications

(76 reference statements)

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“…These benefits are likely to be linked to cellular changes in the hippocampus, including angiogenesis (Van der Borght et al, 2009), neurogenesis and the release of neurotrophins (Neeper et al, 1996, Kitamura et al, 2003), but are also influenced by stressors (Stranahan et al, 2006, Hare et al, 2012, Onksen et al, 2012) that induce neurogenesis-dependent anxiety (Fuss et al, 2010, Onksen et al, 2012). For humans, dieting is one stressor that is often combined with exercise.…”

Section: Discussionmentioning

confidence: 99%

α4βδ-GABAARs in the hippocampal CA1 as a biomarker for resilience to activity-based anorexia

et al. 2014

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Anorexia nervosa (AN) is a psychiatric illness characterized by restricted eating and an intense fear of gaining weight. Most individuals with AN are females, diagnosed first during adolescence, 40% to 80% of whom exhibit excessive exercise, and an equally high number with a history of anxiety disorder. We sought to determine the cellular basis for individual differences in AN vulnerability by using an animal model, activity-based anorexia (ABA), that is induced by combining food restriction (FR) with access to a running wheel that allows voluntary exercise. Previously, we showed that by the 4th day of FR, the ABA group of adolescent female rats exhibit > 500% greater levels of non-synaptic α4βδ−GABAARs at the plasma membrane of hippocampal CA1 pyramidal cell spines, relative to the levels found in age-matched controls that are not FR and without wheel access. Here, we show that the ABA group exhibits individual differences in body weight loss, with some losing nearly 30%, while others lose only 15%. The individual differences in weight loss are ascribable to individual differences in wheel activity that both precedes and concurs with days of FR. Moreover, the increase in activity during FR correlates strongly and negatively with α4βδ−GABAAR levels (R= - 0.9, p<0.01). This negative correlation is evident within 2 days of FR, before body weight loss approaches life-threatening levels for any individual. These findings suggest that increased shunting inhibition by α4βδ−GABAARs in spines of CA1 pyramidal neurons may participate in the protection against the ABA-inducing environmental factors of severe weight loss by suppressing excitability of the CA1 pyramidal neurons which, in turn, is related indirectly to suppression of excessive exercise. The data also indicate that, although exercise has many health benefits, it can be maladaptive to individuals with low levels of α4βδ−GABAARs in the CA1, particularly when combined with FR.

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Section: Discussionmentioning

confidence: 99%

α4βδ-GABAARs in the hippocampal CA1 as a biomarker for resilience to activity-based anorexia

et al. 2014

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“…The NIH test is a well-validated model of anxiety-like behavior in mice (Balu et al, 2013;Bechtholt et al, 2007a, b;Dulawa and Hen, 2005;Gamble-George et al, 2013;Goeldner et al, 2012;Gur et al, 2007;Merali et al, 2003;Onksen et al, 2012;Turner et al, 2010), which is sensitive to acute treatment with anxiolytic drugs, such as chlordiazepoxide (Merali et al, 2003;Turner et al, 2010), but not acute treatment with antidepressants (Gur et al, 2007;Santarelli et al, 2003). One week before training and for the duration of the experiment, mice were housed in groups of two.…”

Section: Nih Testmentioning

confidence: 99%

“…To model this pre-clinically, we utilized the NIH test, a well-validated model of anxiety-like behavior in mice (Balu et al, 2013;Bechtholt et al, 2007a, b;Dulawa et al, 2005;Goeldner et al, 2012;Gur et al, 2007;Merali et al, 2003;Onksen et al, 2012;Turner et al, 2010). Animals chronically treated with nicotine show a reduced latency to feed in a novel environment relative to saline controls, indicating an anxiolytic response (Figure 1) (Turner et al, 2010).…”

Section: Withdrawal From Chronic Nicotine Elicits An Anxiogenic Effecmentioning

confidence: 99%

Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal

Turner

Wilkinson

Poole

et al. 2013

Neuropsychopharmacol

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Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that o10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective a4b2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxietyrelated behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated with their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.

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“…There is mounting evidence that exercise protects against the deleterious effects of chronic stress (Droste et al, 2003; Greenwood and Fleshner, 2008; Onksen et al, 2012). Perhaps by providing an alternative coping strategy regular physical activity has been shown to effectively prevent and treat stress-related disorders including anxiety (Manger and Motta, 2005), depression (Babyak et al, 2000; Knubben et al, 2007), and substance abuse (Zschucke et al, 2012).…”

mentioning

confidence: 99%

Oral Self‐Administration of EtOH: Sex‐Dependent Modulation by Running Wheel Access in C57BL/6J Mice

Piza-Palma

Barfield

Brown

et al. 2014

Alcoholism Clin & Exp Res

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Background The effects of stress, including neuroendocrine and behavioral sequelae aimed at maintaining homeostasis, are associated with increased alcohol consumption. Because both stress and drinking are multifactorial, the mechanisms underlying the relationship are difficult to elucidate. We therefore employed an animal model investigating the influence of blocked access to a running wheel on drinking in C57BL/6J (B6) mice. Methods In the first experiment, naïve, adult male and female subjects were individually housed for 2 weeks with 24hr access to a running wheel and 12% EtOH in a 2-bottle, free choice paradigm. After determining baseline consumption and preference, experimental subjects had the running wheel placed in a locked position for 6hr, and the EtOH bottle was removed during the first half of this period. Two subsequent experiments, again in adult, naïve B6 mice, examined the influence of locked running wheels on self-administration of 20% EtOH in a limited access paradigm, and blood EtOH concentrations (BECs) were determined. Results In all three studies, using both between and within subject analyses, females showed transient yet reliable increases in alcohol drinking during blocked access to a rotating activity, while drinking in male mice was largely insensitive to this manipulation, though both sexes showed appreciable BECs (>130 mg/dL in females, and 80 mg/dL in males) following a 2hr EtOH access period. Conclusions These data add to a burgeoning literature suggesting that the factors contributing to excessive alcohol use differ between males and females, and that females may be especially sensitive to the influence of wheel manipulation. Elucidating the sex-dependent mechanisms mediating differences in alcohol sensitivity and response is critical to understanding the causes of alcoholism and in developing effective treatments and interventions.

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Running‐induced anxiety is dependent on increases in hippocampal neurogenesis

Cited by 25 publications

References 51 publications

α4βδ-GABAARs in the hippocampal CA1 as a biomarker for resilience to activity-based anorexia

α4βδ-GABAARs in the hippocampal CA1 as a biomarker for resilience to activity-based anorexia

Divergent Functional Effects of Sazetidine-A and Varenicline During Nicotine Withdrawal

Oral Self‐Administration of EtOH: Sex‐Dependent Modulation by Running Wheel Access in C57BL/6J Mice

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