Early social isolation disrupts latent inhibition and increases dopamine D2 receptor expression in the medial prefrontal cortex and nucleus accumbens of adult rats
ABSTRACT Adolescence is a critical period for neurodevelopment. In the present study, we investigated the effects of peri-adolescent social isolation on latent inhibition (LI) and dopamine D2 receptor expression in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) of young adult rats. Male Sprague-Dawley rats were randomly divided into adolescent isolation (ISO; isolated housing, 21-34 days of age) and social housing (SOC) groups. LI was tested at postnatal day 56. After behavioral testing, the number of dopamine D2 receptor-expressing cells was determined using immunohistochemistry. Adolescent social isolation impaired LI and increased the number of cells expressing the D2 receptor in the mPFC and NAc. The results suggest that adolescent social isolation produces profound effects on cognitive and dopaminergic function in adult rats, and could be used as an animal model of various neurodevelopmental disorders.
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ABSTRACT: This article is part of a Special Issue "Puberty and Adolescence". Learning and memory is affected by a myriad of factors, including exposure to stressors and the corresponding rise in circulating glucocorticoids. Nevertheless, the effects of stressors depend on the sex, species, the type of stressor used, the duration of exposure, as well as the developmental time-point in which stressors are experienced. Effects of stress in adolescence, however, have received less attention than other developmental periods. In adolescence, the hypothalamic-pituitary-adrenal axis and brain regions involved in learning and memory, which also richly express corticosteroid receptors, are continuing to develop, and thus the effects of stress exposures would be expected to differ from those in adulthood. We conclude from a review of the available literature in animal models that hippocampal function is particularly sensitive to adolescent stressors, and the effects tend to be most evident several weeks after the exposure, suggesting stressors alter the developmental trajectory of the hippocampus.Hormones and Behavior 07/2013; 64(2):364-79. DOI:10.1016/j.yhbeh.2012.09.012 · 4.51 Impact Factor
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ABSTRACT: As an adverse early life experience, maternal separation (MS) induces profound neurochemical, cognitive and emotional dysfunction. Although previous studies have reported that MS affected prepulse inhibition (PPI), anxiety-related behaviors, dopaminergic and serotonergic activity in adult rats, and in the present study, we investigated the effects of repeated (4h/day) maternal separation during postnatal days 1-21 on PPI and anxiety-related behaviors in an elevated plus maze, as well as dopamine D2 receptor (DRD2) and 5-HT1A receptor expression in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus in adolescent rats. Our findings show that repeated MS results in reduced PPI, increased anxiety-related behaviors, decreased DRD2 protein expression in the NAc and hippocampus, and decreased 5-HT1A protein expression in the mPFC and hippocampus in adolescent rats. These data further demonstrate that MS can be used as an animal model of neuropsychiatric disease.Brain research 04/2013; DOI:10.1016/j.brainres.2013.04.026 · 2.83 Impact Factor
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ABSTRACT: Social isolation (SI) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety-like behavior, impaired sensorimotor gating and increased self-administration of addictive substances. These changes are accompanied by alterations in mesolimbic dopamine function, such as increased dopamine and metabolite tissue content, increased dopamine responses to cues and psychostimulants, and increased dopamine neuron burst firing. Using voltammetric techniques, we examined the effects of SI rearing on dopamine transporter activity, vesicular release and dopamine D2-type autoreceptor activity in the nucleus accumbens core. Long-Evans rats were housed in group (GH; 4/cage) or SI (1/cage) conditions from weaning into early adulthood [postnatal day (PD) 28-77]. After this initial housing period, rats were assessed on the elevated plus-maze for an anxiety-like phenotype, and then slice voltammetry experiments were performed. To study the enduring effects of SI rearing on anxiety-like behavior and dopamine terminal function, another cohort of similarly reared rats was isolated for an additional 4 months (until PD 174) and then tested. Our findings demonstrate that SI rearing results in lasting increases in anxiety-like behavior, dopamine release and dopamine transporter activity, but not D2 activity. Interestingly, GH-reared rats that were isolated as adults did not develop the anxiety-like behavior or dopamine changes seen in SI-reared rats. Together, our data suggest that early life stress results in an anxiety-like phenotype, with lasting increases in dopamine terminal function.European Journal of Neuroscience 01/2013; DOI:10.1111/ejn.12113 · 3.67 Impact Factor