Social instability stress in adolescence increases anxiety and reduces social interactions in adulthood in male long–evans rats

Green, Matthew R.; Barnes, Brittany; McCormick, Cheryl M.

doi:10.1002/dev.21077

Cited by 86 publications

(71 citation statements)

References 76 publications

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“…For instance, yohimbine has been shown to reduce open-arm time without altering social interaction (Johnston et al 1988). Several groups have proposed that each assay may underlie distinct aspects of anxiety (File 1995; Fuchs and Fliugge 2006; Green et al 2013; Morley and McGregor 2000). If this is the case, then there may be unique mechanisms underlying elevated plus maze and social interaction.…”

Section: Discussionmentioning

confidence: 99%

Behavioral assessment of acute inhibition of system xc - in rats

et al. 2014

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Rationale Gaps in our understanding of glutamatergic signaling may be key obstacles in accurately modeling complex CNS diseases. System xc− is an example of a poorly understood component of glutamate homeostasis that has the potential to contribute to CNS diseases. Objectives To determine whether system xc− contributes to behaviors used to model features of CNS disease states. Methods In situ hybridization was used to map mRNA expression of xCT throughout the brain. Microdialysis in the prefrontal cortex was used to sample extracellular glutamate levels; HPLC was used to measure extracellular glutamate and tissue glutathione concentrations. Acute administration of sulfasalazine (8–16 mg/kg, IP) was used to decrease system xc− activity. Behavior was measured using attentional set shifting, elevated plus maze, open-field maze, Porsolt swim test, and social interaction paradigm. Results The expression of xCT mRNA was detected throughout the brain, with high expression in several structures including the basolateral amygdala and prefrontal cortex. Doses of sulfasalazine that produced a reduction in extracellular glutamate levels were identified and subsequently used in the behavioral experiments. Sulfasalazine impaired performance in attentional set shifting, reduced the amount of time spent in an open arm of an elevated plus maze and the center of an open-field maze without altering behavior in a Porsolt swim test, total distance moved in an open-field maze, or social interaction. Conclusions The widespread distribution of system xc− and involvement in a growing list of behaviors suggests that this form of nonvesicular glutamate release is a key component of excitatory signaling.

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Section: Discussionmentioning

confidence: 99%

Behavioral assessment of acute inhibition of system xc - in rats

et al. 2014

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“…Social interaction between rats was measured using a modified version of protocol similar to one described previously (Golden et al, 2011; Green et al, 2013a). On Day 1, the subject rat, (VPA or saline exposed rat) was habituated to the empty social interaction apparatus (61 × 61 cm gray box) for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

Banerjee

Sauls

Morales

et al. 2014

Front. Behav. Neurosci.

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Autism Spectrum Disorders (ASD) are complex neurodevelopmental disorders characterized by repetitive behavior and impaired social communication and interactions. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety and some ASD individuals exhibit impaired emotional learning. We therefore sought to further examine anxiety and emotional learning in an environmentally induced animal model of ASD that utilizes the administration of the known teratogen, valproic acid (VPA) during gestation. Specifically we exposed dams to one of two different doses of VPA (500 and 600 mg/kg) or vehicle on day 12.5 of gestation and examined the resultant progeny. Our data indicate that animals exposed to VPA in utero exhibit enhanced anxiety in the open field test and normal object recognition memory compared to control animals. Animals exposed to 500 mg/kg of VPA displayed normal acquisition of auditory fear conditioning, and exhibited reduced extinction of fear memory and normal litter survival rates as compared to control animals. We observed that animals exposed to 600 mg/kg of VPA exhibited a significant reduction in the acquisition of fear conditioning, a significant reduction in social interaction and a significant reduction in litter survival rates as compared to control animals. VPA (600 mg/kg) exposed animals exhibited similar shock sensitivity and hearing as compared to control animals indicating the fear conditioning deficit observed in these animals was not likely due to sensory deficits, but rather due to deficits in learning or memory retrieval. In conclusion, considering that progeny from dams exposed to rather similar doses of VPA exhibit striking differences in emotional learning, the VPA model may serve as a useful tool to explore the molecular and cellular mechanisms that contribute to not only ASD, but also emotional learning.

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“…Similar to humans, early adolescence is a critical time period for rodents. Rats that have been socially isolated (SI) during adolescence spend less time on the open arm of an elevated plus maze (Hall et al, 1998; McCool and Chappell, 2009), display reduced social interaction (Green et al, 2012), and increased immobility during the forced swim test compared to group housed (GH) rats (Kokare et al, 2010), exemplifying anxiety- and depression-like phenotypes. SI rats also show pre-pulse inhibition deficits (Han et al, 2012) and reduced habituation to an open field (Lapiz et al, 2000) demonstrating a reduced ability to adapt to environmental changes.…”

Section: Introductionmentioning

confidence: 99%

Social Isolation Rearing Increases Nucleus Accumbens Dopamine and Norepinephrine Responses to Acute Ethanol in Adulthood

Karkhanis

Locke

McCool

et al. 2014

Alcoholism Clin & Exp Res

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BACKGROUND Early-life stress is associated with increased vulnerability to alcohol addiction. However, the neural substrates linking chronic childhood/adolescent stress and increased risk of alcohol addiction are not well understood. In the nucleus accumbens (NAc), dopamine (DA) and norepinephrine (NE) signaling can be profoundly influenced by stress, anxiety, and drugs of abuse, including ethanol. Here, we employed a rodent model of early-life stress that results in enduring increases in behavioral risk factors of alcoholism to gain a better understanding of how chronic adolescent stress may impact the ethanol sensitivity of DA and NE release in the NAc. METHODS Male Long Evans rats were either group housed (GH; 4 rats/cage) or socially isolated (SI; 1 rat/cage) for six weeks beginning on postnatal day 28. SI and GH rats were tested in adulthood for anxiety-like behaviors (elevated plus-maze), and the effects of ethanol (1 and 2 g/kg; i.p.) on NAc DA and NE were assessed by microdialysis. RESULTS SI animals showed increased anxiety-like behavior compared to GH animals. Although SI had no effect on baseline levels of DA or NE, baseline DA levels were positively correlated with anxiety measures. In addition, while no significant differences were observed with 1 g/kg ethanol, the 2 g/kg dose induced significantly greater DA release in SI animals. Moreover, EtOH (2 g/kg) only elevated NAc NE levels in SI rats. CONCLUSIONS These results suggest that chronic early-life stress sensitizes accumbal DA and NE release in response to an acute ethanol challenge. A greater EtOH sensitivity of DA and NE release dynamics in the NAc may contribute to increases in behavioral risk factors of alcoholism, like greater ethanol self-administration, that are observed in SI rats.

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Social instability stress in adolescence increases anxiety and reduces social interactions in adulthood in male long–evans rats

Cited by 86 publications

References 76 publications

Behavioral assessment of acute inhibition of system xc - in rats

Behavioral assessment of acute inhibition of system xc - in rats

Abnormal emotional learning in a rat model of autism exposed to valproic acid in utero

Social Isolation Rearing Increases Nucleus Accumbens Dopamine and Norepinephrine Responses to Acute Ethanol in Adulthood

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