Neuroscience
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Disruption of the glucocorticoid negative feedback system is observed in approximate one half of human depressives, and a similar condition is induced in animals by chronic stress. This disruption is thought to involve down-regulation of glucocorticoid receptors (GRs) in the feedback sites of the brain. However, the responsible site of the brain has not been well elucidated. ⋯ In addition, when DEX was injected systemically to the chronically stressed rats, the suppressive response to DEX was significantly attenuated. These results suggest that the abnormal changes in GRs in the higher centers of the hypothalamo-pituitary-adrenal axis are involved in the chronic stress-induced attenuation of the feedback. Since dysfunction of the PFC or hippocampus is implicated in the pathogenesis of depression, the present findings would help to understand the mechanisms underlying the disrupted feedback system and its relation to brain dysfunction in depression.
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Brain-derived neurotrophic factor (BDNF) expression in the hippocampus is reduced in response to acute, as well as repeated immobilization stress. This effect might be mediated by corticosterone, because corticosterone administration is known to reduce hippocampal BDNF. ⋯ To dissect the relative contributions of learning and stress to the overall changes in BDNF levels we set up an experimental model in which two groups of rats received the same amount of stress, but only one group had the possibility to learn how to avoid it. Using this model, we now report that learning and stress exert an opposite modulation on BDNF levels in the hippocampus, and that the increasing effect of learning predominates over the decreasing effect of stress.
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Comparative Study
Heterogeneous expression of the cholecystokinin-like immunoreactivity in the mouse hippocampus, with special reference to the dorsoventral difference.
The neuropeptide cholecystokinin (CCK) is widely distributed in the CNS. We herein investigated the immunocytochemical localization of CCK in the glutamatergic excitatory pathways in the mouse hippocampus, with particular reference to the dorsoventral difference. The intense CCK-like immunoreactivity (CCK-LI) was found in the mossy fiber pathway (stratum lucidum and dentate hilus) and in the inner molecular layer of the dentate gyrus. ⋯ Interestingly, the distributions of the SPO immunoreactivity at P 7 were already similar to those of adult mice. The patterns of expression of CCK-LI at P 28 were almost similar to those of adult mice. The present data demonstrate the heterogeneous expression of CCK-LI in the mouse hippocampus, and provide a baseline to understand the role of CCK in the mouse brain.
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Changes in kappa-opioid receptor levels have been implicated in the development of physical dependence upon and withdrawal from the mixed agonist-antagonist opioid, butorphanol. Immunoblotting analysis was performed to determine the levels of kappa- and mu-opioid receptors in brain regions of rats in withdrawal from dependence upon butorphanol or morphine. Physical dependence was induced by a 72 h i.c.v. infusion with either butorphanol or morphine (26 nmol/microl/h). ⋯ These findings contrasted with those from morphine-withdrawal rats, in which the only changes noted were increases in the thalamus and paraventricular thalamus. Changes in the levels of the mu-opioid receptor protein were observed in 11 of 21 brain regions examined in morphine-withdrawal rats, but only in three of 21 in butorphanol-withdrawal rats. These results implicate a substantive and largely unique role for kappa-opioid receptors in mediation of the development of physical dependence upon, and the expression of withdrawal from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.
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Traumatic brain injury (TBI) initiates immediate and secondary neuropathological cascades that can result in persistent neurological dysfunction. Previous studies from our laboratory have shown that experimental rat brain injury causes a rapid and persistent decrease in CNS alpha7* nicotinic cholinergic receptor (nAChr) expression. The purpose of this study was to investigate whether intermittent nicotine injections could improve cognitive performance in the Morris water maze (MWM) following experimental brain injury. ⋯ TBI caused significant deficits in alpha7* nAChr expression in several regions of the hippocampus and cerebral cortex, which were largely unaffected by intermittent nicotine treatment. However, nicotine treatment up-regulated [(3)H]-epibatidine binding to non-alpha7* nAChrs, attenuating TBI-induced deficits in receptor expression in several brain regions evaluated. These results suggest that nicotine is efficacious at attenuating CCI-induced cognitive deficits in a manner independent of changes in alpha7* nAChr expression, perhaps via up-regulation of non-alpha7* nAChrs.