Behavioural brain research
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Nitric oxide (NO) is sought to be an intracellular messenger in the central nervous system and its implication in learning and memory is well documented. Compounds that inhibit nitric oxide synthase (NOS), the key synthesizing enzyme, block cognition, though discrepant findings, in this context, have also been reported. ⋯ Subsequently, l-NAME (1 and 10, but not 3mg/kg)-treated rats were capable to antagonize delay-dependent deficits, which instead were present in the vehicle-treated animals. These results indicate that repeated administration of this NOS inhibitor exerts a dual effect on rats' recognition memory abilities suggesting a complex involvement of l-NAME in cognition.
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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.
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Evidence suggests that the heterozygous transmembrane domain mutant mouse model for the schizophrenia candidate gene neuregulin 1 (Nrg1 HET) exhibits a deficit in prepulse inhibition (PPI). However, not all mouse models for Nrg1 exhibit PPI deficits. Thus, our study intended to clarify the severity of the initially described PPI deficit in Nrg1 HET mice. ⋯ In conclusion, the often-noted PPI phenotype of the transmembrane domain Nrg1 mutant mouse model is highly PPI protocol-specific and appears sensitive to the particular conditions of the test laboratory. Our study describes wild type-like PPI under most test conditions and across three different laboratories. The research suggests that analysing one of the alleged hallmarks of animal models for schizophrenia must be done carefully: to obtain reliable PPI data it seems necessary to use more than one particular PPI protocol.
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Comparative Study
Morphological and neuro-behavioral parallels in the rat model of stroke.
Middle cerebral artery occlusion (MCAO) is widely used as a rat model of focal brain ischemia. Evaluation of brain damage often includes the morphological analysis of the injury area, MRI, and various scales which depend on functional tests, commonly known as neurological severity score (NSS). We determined the optimal number of NSS tests and assessed their capacity for non-invasive evaluation of brain ischemic injury in the rat MCAO model. 275 male Sprague-Dawley rats were randomly divided into five groups, given either permanent (p) MCAO or transient (t) MCAO using an uncoated 4-0 monofilament catheter or a silicone-coated monofilament. ⋯ The Hosmer-Lemeshow p-value of this model was 0.558 for brain edema. Our methods of estimating infarct size produces reliable and well correlated results at 24h and demonstrates to be an easy and quick way to assess infarct size soon after ischemic injury has occurred. The described method for neurological assessment could ultimately aid in assessing various treatment modalities in the early hours following stroke.
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The paucity of appropriate animal models for bipolar disorder hinders the research of the disorder and its treatments. Previous work suggests that Black Swiss (BS) mice may be a suitable model animal for behavioral domains of mania including reward-seeking, risk-taking, vigor, aggression and sensitivity to psychostimulants. These behaviors are high in BS mice compared with other strains and are responsive to the mood stabilizers lithium and valproate but not to the antidepressant imipramine. ⋯ BDNF expression levels were similar between strains in both the hippocampus and frontal cortex. In the behavioral tests, risperidone ameliorated amphetamine-induced hyperactivity without affecting other tests in the battery. These results offer additional pharmacological and possible etiological validity supporting the utilization of Black Swiss mice as a model for domains of mania.