Peripubertal stress-induced behavioral changes are associated with altered expression of genes involved in excitation and inhibition in the amygdala

Tzanoulinou, Stamatina; Riccio, Orbicia; Boer, Mark Walther; Sandi, Carmen

doi:10.1038/tp.2014.54

Cited by 79 publications

(74 citation statements)

References 83 publications

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“…Specifically, adolescent social defeat resulted in decreased levels of NMDA receptors in both the central nucleus of the amygdala (CeA) and the infralimbic region of the mPFC, while increased NMDA receptor expression was noted in the CA3 region of the hippocampus. Several other studies have looked at NMDA receptor expression in response to stress, albeit utilizing different quantification methods, developmental time points, and stress procedures [10, 11, 39–45]. While the majority of these studies looked at expression of specific NMDA receptor subunits, one study measuring 3H-MK-801 binding immediately following repeated immobilization stress in adolescent mice found an increase in NMDA expression in the lateral septum and dentate gyrus, but no other regions [10].…”

Section: Discussionmentioning

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Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood

Novick

Mears

Forster

et al. 2016

Behavioural Brain Research

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Repeated social defeat of adolescent male rats results in adult mesocortical dopamine hypofunction, impaired working memory, and increased contextual anxiety-like behavior. Given the role of glutamate in dopamine regulation, cognition, and fear and anxiety, we investigated potential changes to N-methyl-D-aspartic acid (NMDA) receptors following adolescent social defeat. As both NMDA receptors and mesocortical dopamine are implicated in the expression and extinction of conditioned fear, a separate cohort of rats was challenged with a classical fear conditioning paradigm to investigate whether fear learning is altered by adolescent defeat. Quantitative autoradiography was used to measure 3H-MK-801 binding to NMDA receptors in regions of the medial prefrontal cortex, caudate putamen, nucleus accumbens, amygdala and hippocampus. Assessment of fear learning was achieved using an auditory fear conditioning paradigm, with freezing towards the auditory tone used as a measure of conditioned fear. Compared to controls, adolescent social defeat decreased adult NMDA receptor expression in the infralimbic region of the prefrontal cortex and central amygdala, while increasing expression in the CA3 region of the hippocampus. Previously defeated rats also displayed decreased conditioned freezing during the recall and first extinction periods, which may be related to the observed decreases and increases in NMDA receptors within the central amygdala and CA3, respectively. The alteration in NMDA receptors seen following adolescent social defeat suggests that dysfunction of glutamatergic systems, combined with mesocortical dopamine deficits, likely plays a role in the some of the long-term behavioral consequences of social stressors in adolescence seen in both preclinical and clinical studies.

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Section: Discussionmentioning

(Expert classified)

Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood

Novick

Mears

Forster

et al. 2016

Behavioural Brain Research

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“…Alterations in the magnitude of stress-induced glucocorticoid responses can have both immediate effects in brain function through non-genomic mechanisms and long-term effects mediated by changes in gene transcription; however, the latter mechanism is predominantly involved when basal glucocorticoid levels are affected [64][65][66][67][68][69] . These changes in glucocorticoid levels seem to contribute to many of the changes in social behaviors induced by stressors.…”

Section: Changes In Glucocorticoid Levels In Stress Modelsmentioning

confidence: 99%

“…Other studies have mimicked the long-term effects of early stress exposure on HPA-axis function. For example, acute glucocorticoid treatments in adulthood that mimicked the HPA-axis alterations resulting from post-weaning social isolation decreased sociability and social behavior and increased aggression 69,72 . In another example, mimicking the reduction in HPA axis activity in adulthood caused by early deprivation, early subjugation and non-social peripubertal stressors (through adrenalectomy with low-level glucocorticoid replacement) 72 led to decreased social behaviors and antisociality.…”

Section: Effects Of Manipulating Glucocorticoid Levelsmentioning

confidence: 99%

Stress and the social brain: behavioural effects and neurobiological mechanisms

2015

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“…Likewise, using an alternating series of physical stressors (elevated platform, water immersion or footshock on different days) instead of social isolation, stressor exposure from P22-33 was observed to increase anxiety-like behavior in the elevated plus maze and probe burying task; these effects were more pronounced in males and were not evident with stressor exposure from P35-46 (Wilkin et al, 2012). Exposure to two variable stressors (fox odor; exposure to an elevated platform) from P28-42 was reported to induce deficits in sociability, increased aggression and novelty reactivity, and to alter expression of genes influencing excitatory-inhibitory balance in the amygdala (Tranoulinou et al, 2014). These effects were not evident when the stressor period was from P28-30 or P40-42; whether these differences reflect stressor timing versus duration of the stressor period is unclear.…”

Section: Animal Studiesmentioning

confidence: 99%

Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

Spear

2015

Physiology & Behavior

222

189

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There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing-specific exposure effects, notable maturational changes in brain have been observed from early to late adolescence that could provide differential neural substrates for exposure timing-related consequences, with for instance exposure during early adolescence perhaps more likely to impact later self-administration and social/affective behaviors, whereas exposures later in adolescence may be more likely to influence cognitive tasks whose neural substrates (such as the prefrontal cortex [PFC]) are still undergoing maturation at that time. Substantial more work is needed, however to characterize timing-specific effects of adolescent ethanol exposures and their sex dependency, determine their neural substrates, and assess their comparability to and interactions with adolescent exposure to other drugs and stressors. Such information could prove critical for informing intervention/prevention strategies regarding the potential efficacy of efforts directed toward delaying onset of alcohol use versus toward reducing high levels of use and risks associated with that u...

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Peripubertal stress-induced behavioral changes are associated with altered expression of genes involved in excitation and inhibition in the amygdala

Cited by 79 publications

References 83 publications

Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood

Adolescent social defeat alters N-methyl-d-aspartic acid receptor expression and impairs fear learning in adulthood

Stress and the social brain: behavioural effects and neurobiological mechanisms

Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

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