Behavioural brain research
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Many patients with chronic inflammatory disorders have an abnormal high prevalence of major depression accompanied by elevated levels of tumor necrosis factor-α (TNF-α). We hypothesize that systemic TNF-α increases brain monoamine metabolism, which might induce anhedonia (i.e. a core symptom of major depression). The effect of an intraperitoneal TNF-α injection on extracellular monoamine and metabolite concentrations was investigated by in vivo microdialysis in the nucleus accumbens (NAc) of C57BL/6 mice. ⋯ Remarkably, TNF-α also increased the dopamine metabolite HVA, without affecting dopamine levels itself. These data concur with earlier findings that pro-inflammatory cytokines enhance serotonin transporter activity, and possibly also dopamine transporter activity in the brain. However, more research is needed to understand the precise molecular mechanisms by which TNF-α increases transporter activity and anhedonia.
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The study of individual differences provides an important methodological approach to analyze the neurobehavioral spectrum of a given cohort in order to understand brain function and disease. Based on immobility time in the forced swimming test (FST) juvenile and adult rats were classified as subgroups with low and high immobility. Afterwards, we compared behavior, neurochemical parameters, and gene expression profiles in some brain areas of rats with low and high immobility only. ⋯ Moreover, the expression of accumbal corticotrophin-releasing factor receptor 1 (CRFR1) was significantly different in animals with low and high immobility at both ages, with animals less immobile showing higher levels of CRFR1 mRNA levels. Taken together, our findings suggest that differences in monoaminergic neurotransmission and CRFR1 expression are associated with the coping strategy adopted by the animal and with the tendency to develop depression-related behaviors. Concerning monoaminergic neurotransmission such association is modulated by age, and such modulation could be related to the differential behavioral results observed between juvenile and adult rats.
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Anandamide and 2-arachidonoylglycerol (2-AG) are the two main endocannabinoids, exerting their effects by activating type 1 (CB1r) and type 2 (CB2r) cannabinoid receptors. Anandamide inhibits anxiety-like responses through the activation of CB1r in certain brain regions, including the dorsolateral periaqueductal gray (dlPAG). 2-AG also attenuates anxiety-like responses, although the neuroanatomical sites for these effects remained unclear. Here, we tested the hypothesis that enhancing 2-AG signaling in the dlPAG would induce anxiolytic-like effects. ⋯ These behavioral responses were prevented by CB1r (AM251) or CB2r (AM630) antagonists. Our results showed that the augmentation of 2-AG levels in the dlPAG induces anxiolytic-like effects. The mechanism seems to involve both CB1r and CB2r receptors.
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Environmental enrichment attenuates the response to psychostimulants and has been shown to reduce both anxiety and stress-related behaviors. Since stress is a major vulnerability factor for addiction, we investigated whether enrichment could reverse stress profiles in high anxious rats as well as reduce their amphetamine sensitivity. Using selectively-bred high and low anxiety males (filial 3) from enriched, social or isolated environments, we tested elevated plus maze exploration, novelty place preference and amphetamine (AMPH; 0.5mg/kg, IP)-induced hyperactivity. ⋯ There were no group differences or interactions found for novelty place preference. Enriched environments decreased the response to AMPH and stress-induced CORT regardless of trait but selectively decreased pTrkB and increased D2 mRNA levels in high anxiety animals. The results suggest that selectively-bred trait anxiety rats show state anxiety that is influenced by rearing environments, and D2 protein levels and BDNF/TrkB signaling may differentially contribute to integrating these effects.
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Disrupted white matter (WM) integrity is the pathological hallmark of schizophrenia. Previous studies have reported the cognitive deficits that are associated with WM disruption in schizophrenia with anti-psychiatric treatment. However, no study has yet revealed the correlation between cognition and WM abnormalities in never-medicated chronic schizophrenia. ⋯ Our results provide evidence to support that the disconnection of WM pathways may contribute to the pathophysiology of schizophrenia and suggest that the disturbance of left ILF and left IFOF integrity may contribute to cognitive deficits in schizophrenia, independent of effects of antipsychotic medication.