The effects of chronic antidepressant treatment in an animal model of anxiety

Bodnoff, Shari R.; Suranyi-Cadotte, Barbara E.; Aitken, David H.; Quirion, Rémi; Meaney, Michael J.

doi:10.1007/bf00181937

Cited by 384 publications

(231 citation statements)

References 32 publications

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“…3A). In the novelty suppressed feeding test (28)(29)(30), AAV-Nrn significantly decreased the latency to feed, similar to the actions of antidepressant treatments ( Fig. 3B; P < 0.05 compared with AAV-ctl).…”

Section: Neuritin Increases Hippocampal Dendrite Complexity and Spinesupporting

confidence: 66%

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

Son

Banasr

Choi³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors.is a devastating and recurrent illness affecting up to 17% of the population, resulting in personal disability, increased rates of suicide, and socioeconomic loss (1). Moreover, currently available antidepressants are only effective in approximately one-third of patients with MDD and in up to two-thirds after multiple trials, and they take weeks to months to produce a response (2, 3). In addition, the mechanisms underlying the therapeutic actions of antidepressants are poorly understood. New targets beyond monoamine signaling are now emerging in both preclinical and clinical reports of MDD (4, 5). These studies have focused on key limbic brain structures, including the hippocampus, that are significantly altered by chronic stress and depression and that are known to regulate mood, anxiety, and cognition (6, 7). Hippocampal synaptic plasticity has received much attention in recent years because human imaging and rodent studies demonstrate that stress and depression are associated with decreased hippocampal volume and atrophy of neurons (6,8).Neuritin, also known as candidate plasticity gene 15 (CPG15), encodes a small, extracellular GPI-anchored protein critical for dendritic outgrowth, maturation, and axonal regeneration (9-13). Neuritin expression in the hippocampus is induced by neuronal activity following chemical-or electrical-induced seizures (9, 14, 15), ischemia (16), and exercise (5, 17). Neuritin has been implicated in the actions of BDNF (9, 18), which is up-regulated in the hippocampus by antidepressant treatment and is sufficient to produce antidepressant behavioral responses (19,20). Moreover, chronic antidepressant treatment has been shown to increase neuritin expression in rat brain (21). The current study was conducted to test the hypothesis that neuritin is a critical downstream mediator of antidepressant/BDNF-mediated plasticity and, conversely, that loss of neuritin could contribute to depre...

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Section: Neuritin Increases Hippocampal Dendrite Complexity and Spinesupporting

confidence: 66%

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

Son

Banasr

Choi³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…34 In 1988, Bodnoff et al 35 validated the novelty suppressed feeding (NSF) test. In this model, animals deprived of food for 24 hours are exposed to a transparent box consisting of a sawdust-covered floor, a central platform holding a single pellet of chow, and focused lighting.…”

Section: Hyponeophagia-based Model: Novelty Suppressed Feeding Testmentioning

confidence: 99%

“…Due to this characteristic, the NSF is often employed after the chronic unpredictable stress procedure (where animals are exposed to daily different stressors for, at least, 14 days), which increases anxietylike behaviors, to evaluate the anxiolytic and antidepressant properties of chronic treatments. 35,37 Although it involves hunger, this test is well accepted since it does not require painful procedures or previous training.…”

Section: Hyponeophagia-based Model: Novelty Suppressed Feeding Testmentioning

confidence: 99%

Animal models of anxiety disorders and stress

Campos

Fogaça

Aguiar

et al. 2013

Rev. Bras. Psiquiatr.

378

246

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Anxiety and stress-related disorders are severe psychiatric conditions that affect performance in daily tasks and represent a high cost to public health. The initial observation of Charles Darwin that animals and human beings share similar characteristics in the expression of emotion raise the possibility of studying the mechanisms of psychiatric disorders in other mammals (mainly rodents). The development of animal models of anxiety and stress has helped to identify the pharmacological mechanisms and potential clinical effects of several drugs. Animal models of anxiety are based on conflict situations that can generate opposite motivational states induced by approach-avoidance situations. The present review revisited the main rodent models of anxiety and stress responses used worldwide. Here we defined as ''ethological'' the tests that assess unlearned/unpunished responses (such as the elevated plus maze, light-dark box, and open field), whereas models that involve learned/ punished responses are referred to as ''conditioned operant conflict tests'' (such as the Vogel conflict test). We also discussed models that involve mainly classical conditioning tests (fear conditioning). Finally, we addressed the main protocols used to induce stress responses in rodents, including psychosocial (social defeat and neonatal isolation stress), physical (restraint stress), and chronic unpredictable stress.

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“…NSF measures a rodent's aversion to eating in a novel environment, specifically assessing stress-induced anxiety by measuring the latency of the mouse to eat a familiar food in a novel, aversive environment (Bodnoff et al, 1988). This trait has been shown in rats to be sensitive to early-life interventions.…”

Section: Effects Of Js and Autoreceptor Knockdown Are Dissociable In mentioning

confidence: 99%

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

Donaldson

Piel

Santos

et al. 2013

Neuropsychopharmacol

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The serotonin 1A receptor (5-HT1A) has a major role in modulating the effects of serotonin on mood and behavior. Previous studies have shown that knockout of 5-HT1A selectively in the raphe leads to higher levels of anxiety during adulthood. However, it remains unclear whether this phenotype is due to variation in receptor levels specifically during development or throughout life. To test the hypothesis that developmental sensitivity may underlie the effects of 5-HT1A on anxiety, we used an inducible transgenic system to selectively suppress 5-HT1A levels in serotonergic raphe neurons from post-natal days (P) 14 to P30, with a maximal reduction of 40% at P21 and return to regular levels by P30. This developmental decrease in receptor levels has long-lasting consequences, increasing anxiety and decreasing social investigation in adulthood. In addition, post-natal knockdown of autoreceptors leads to long-term increases in the excitability of serotonergic neurons, which may represent a mechanism underlying the effects of post-natal receptor variation on behavior later in life. Finally, we also examined the interplay between receptor variation and juvenile exposure to stress (applied from P14 to P21). Similar to receptor knockdown, juvenile exposure to stress led to increased anxiety phenotypes but did not exacerbate 5-HT1A knockdown-mediated anxiety levels. This work indicates that the effects of 5-HT1A autoreceptors on anxiety and social behaviors are developmentally mediated and suggests that natural variations in the expression of 5-HT1A may act during development to influence individual anxiety levels and contribute to susceptibility to anxiety disorders.

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The effects of chronic antidepressant treatment in an animal model of anxiety

Cited by 384 publications

References 32 publications

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

Animal models of anxiety disorders and stress

Developmental Effects of Serotonin 1A Autoreceptors on Anxiety and Social Behavior

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