Behavioural brain research
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Neuregulin 1 (NRG1) is an important growth factor involved in the development and plasticity of the central nervous system. Since its identification as a susceptibility gene for schizophrenia, several transgenic mouse models have been employed to elucidate the role NRG1 may play in the pathogenesis of psychiatric disease. Unfortunately very few studies have included females, despite the fact that some work suggests that the consequences of disrupted NRG1 expression may be sex-specific. ⋯ Furthermore, we also show that female, but not male, Nrg1(Tn) rats have impaired prepulse inhibition. Finally, we provide evidence that sex-specific changes are not likely attributable to major disruptions in the hypothalamic-pituitary-gonadal axis, as measures of pubertal onset, estrous cyclicity, and reproductive capacity were unaltered in female Nrg1(Tn) rats. Our results provide further support for both the involvement of NRG1 in the control of hypothalamic-pituitary-adrenal axis function and the sex-specific nature of this relationship.
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Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B(3)) in animal models of TBI with systemic dosing at 50 and 500 mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150 mg/kg day) or saline (1 ml/kg) pumps 30 min after CCI, continuing until seven days post-CCI. ⋯ Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies.
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Brain concussion is a serious public health concern and is associated with short-term cognitive impairments and behavioral disturbances that typically occur in the absence of significant brain damage. The current study addresses the need to better understand the effects of a mild lateral fluid percussion injury on rat behavior and neuropathology in an animal model of concussion. Male Long-Evans rats received either a single mild fluid percussion injury or a sham-injury, and either a short (24h) or long (4 weeks) post-injury recovery period. ⋯ Neuropathological analysis of the brains of injured rats showed an acute increase in reactive astrogliosis and activated microglia in cortex and evidence of axonal injury in the corpus callosum. There were no significant long-term effects on any behavioral or neuropathological measure 4 weeks after injury. These short-term behavioral and neuropathological changes are consistent with findings in human patients suffering a brain concussion, and provide further evidence for the use of a single mild lateral fluid percussion injury to study concussion in the rat.
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In this study, the potential antidepressant-like effects of pioglitazone and the possible involvement of peroxisome proliferator-activated receptor gamma (PPARγ) and nitric oxide system in antidepressant effects of pioglitazone were determined using forced swimming test (FST) in mice. ⋯ The antidepressant-like effect of pioglitazone on mice in the FST is mediated at least in part through PPARγ receptors and nitric oxide pathway.
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As in humans, genetic background in rodents may influence a peculiar set of behavioural traits such as sensitivity to pain and stressors or anxiety-related behaviours. Therefore, we tested the hypothesis that mice with different genetic backgrounds [outbred (CD1), inbred (C57BL/6J) and hybrid (B6C3F1) adult male mice] display altered reactivity to pain, stress and anxiety related behaviours. We demonstrated that B6C3F1 mice displayed the more anxious phenotype with respect to C57BL/6J or CD1 animals, with the latter being the less anxious strain when tested in an open field and on an elevated plus maze. ⋯ We then measured intra-strain differences and CFA-induced inter-strain effects on the expression of various genes with a recognized role in pain and anxiety: BDNF, IL-6, IL-1β, IL-18 and NMDA receptor subunits in the mouse thalamus, hippocampus and hypothalamus. The more anxious phenotype observed in B6C3F1 hybrid mice displayed lower levels of BDNF mRNA in the hippocampus and hypothalamus when compared to outbred CD1 and C57BL/6J inbred mice. CFA led to a general decrease in central gene expression of the evaluated targets especially in CD1 mice, while BDNF hypothalamic downregulation stands out as a common effect of CFA in all three strains evaluated.