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.
"In fact, genetic and pharmacologic models of disrupted DA signaling display changes in cortical and striatal circuitry (Stanwood et al., 2001b, 2005; Song et al., 2002; Kellendonk et al., 2006; McCarthy et al., 2007; Zhang et al., 2010). Environmental, social, and inflammatory challenges during sensitive periods of forebrain development also produce neuro(mal)adaptions in these regions and phenocopy some aspects of brain disorders (Di Forti et al., 2007; Kern et al., 2010; Han et al., 2012; Selemon and Friedman, 2013). For example, models of prenatal infection, stress, and exposure to drugs of abuse show long-lasting changes in DA receptor expression and function and have been associated with increased risk for psychiatric disorders (Alonso et al., 1994; Stanwood et al., 2001b; Berger et al., 2002; Zuckerman et al., 2003; Andersen and Teicher, 2009; Bhide, 2009; Brown et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.
"In the hippocampus and medial prefrontal cortex, chronic stress leads to dendritic retraction and a reduction of synapses (e.g., McLaughlin et al., 2007; Radley et al., 2008; Sandi et al., 2003; Wellman, 2001) and impairs signal transduction cascades underlying neural plasticity (e.g., Kuipers et al., 2003). In contrast, in the orbitofrontal cortex and in the basolateral amygdala, chronic stress leads to enhanced dendritic arborization, increased number of dendritic spines, and increased expression of proteins mediating synaptic plasticity (e.g., Lakshminarasimhan and Chattarji, 2012; Liston et al., 2006; Vyas et al., 2002). In terms of behavioural measures, chronic stress typically impairs performance on tests of working memory and of cognitive flexibility (Cerqueira et al., 2007; Dias-Ferreira et al., 2009; Liston et al., 2006; Mizoguchi et al., 2000), impairs spatial maze performance (Conrad et al., 1996; Hutchinson et al., 2012; Luine et al., 1994), and enhances cued and contextual memory of fear conditioning in some studies (reviewed in Rodrigues et al., 2009) or the extinction or renewal of extinction of fear conditioning in other studies (Miracle et al., 2006; Mitra and Sapolsky, 2009). "
[Show abstract][Hide abstract] 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 · 4.63 Impact Factor
"The brains were removed, and the areas of interest (4.70– 0.70 mm from bregma for the mPFC and NAc, −1.30 to −5.30 mm from bregma for the hippocampus, Paxinos and Watson, 1998) were dissected and then post-fixed in 0.01 M PBS containing 4% PFA for 6 h. Next, the samples were rinsed, dehydrated, preembedded , embedded, and sectioned as previously described (Han et al., 2012; Meng et al., 2011). The sections were immersed for 3 Â 5 min in Roti-Histol, followed by 2 Â 5 min in 100% ethanol and 5 min in 96%, 90% and 70% ethanol. "
[Show abstract][Hide abstract] 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; 1518. DOI:10.1016/j.brainres.2013.04.026 · 2.84 Impact Factor
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