Neuroscience
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Central nervous system (CNS) inflammation in cases such as head trauma, infection and stroke has been associated with the occurrence of epileptic seizures. Microglia, the principal immune cells in the brain, readily become activated in response to injury, infection or inflammation. The bacterial endotoxin lipopolysaccharide (LPS) induces the activation of microglia and the production of proinflammatory factors including nitric oxide (NO) and prostaglandins (PGs). ⋯ LPS decreased the seizure threshold in a dose- and time-dependent manner. Pretreatment of mice with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester or cyclooxygenase inhibitor, piroxicam or the opioid receptor antagonist, (-)-naloxone completely reversed the proconvulsant effect of LPS. These results indicate that NO, PGs and endogenous opioid peptides seem to be involved in LPS-induced decrease in seizure threshold.
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The release of dopamine from soma and dendrites of dopaminergic neurons in substantia nigra has been reported to be calcium-dependent, but it remains to be determined which calcium channels mediate this effect. We have used in vivo microdialysis in rat substantia nigra and striatum to investigate the effect of Ca(v)3.1-3.3 (T-type) and Ca(v)2.3 (R-type) calcium channel antagonists on somatodendritic and terminal dopamine release. ⋯ Nickel(II) induced an increase in striatal dialysate dopamine concentration similar to that in substantia nigra. The results indicate a role for Ca(v)2.3 (R-type) voltage sensitive calcium channels in the calcium dependency of somatodendritic dopamine release, but argue against a calcium dependency mediated substantially by Ca(v)3.1-3.3 (T-type) channels.
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Several kinds of stress such as psychological stress, restraint, and foot shock inhibit feeding behavior through corticotropin-releasing factor (CRF). In contrast, a mild tail pinch increases food intake in rats. Although dopamine and opioid are thought to be involved in tail-pinch-induced food intake, it is unknown whether CRF participates in this phenomenon. ⋯ Tail-pinch- or CRF-induced food intake was blocked by naloxone, pimozide, and spiperone. These results suggest that CRF, through CRF receptor type 1 as well as opioid and dopaminergic systems, are involved in the mechanism of tail-pinch-induced food intake. The results also suggest that brain CRF has dual effects on food intake, hyperphagia and anorexia, in a stress-dependent manner.
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Neonatal rats survive and avoid brain injury during periods of anoxia 25 times longer than adults. We hypothesized that oxygen activates and hypoxia suppresses NMDA receptor (NMDAR) responses in neonatal rat neurons, explaining the innate hypoxia tolerance of these cells. In CA1 neurons isolated from neonatal rat hippocampus (mean postnatal age [P] 5.8 days), hypoxia (PO(2) 10 mm Hg) reduced NMDA receptor-channel open-time percentage and NMDA-induced increase in [Ca(2+)](i) (NMDA DeltaCa(2+)) by 38 and 68% (P<0.01), respectively. ⋯ Compared with responses in 21% O(2), hypoxia (PO(2) 17 mm Hg) reduced currents from neonatal type NR1/NR2D receptors by 25%, increased currents from NR1/NR2C by 18%, and had no effect on NR1/NR2A or NR1/NR2B. Modulation of NMDARs by hypoxia may play an important role in the hypoxia tolerance of the mammalian neonate. In addition, oxygen sensing by NMDARs could play a significant role in postnatal brain development.
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Comparative Study
The CRF1 receptor antagonist antalarmin reduces volitional ethanol consumption in isolation-reared fawn-hooded rats.
Corticotropin releasing factor is a neuropeptide associated with the integration of physiological and behavioural responses to stress. More recently, corticotropin releasing factor has been implicated in the actions of abused drugs, including ethanol. Moreover, previous studies have demonstrated that the non-selective corticotropin releasing factor receptor antagonist, alpha-helical corticotropin releasing factor(9-41), can diminish some of the behavioural effects associated with ethanol withdrawal, whilst the selective corticotropin releasing factor(1) receptor antagonist CP-154,526 has been beneficial in decreasing stress-induced relapse into alcohol-seeking behaviour. ⋯ Here we demonstrate that whilst both antalarmin and diazepam can decrease the acquisition of an ethanol-preferring phenotype by Fawn-Hooded rats, only antalarmin can alter established, volitional ethanol consumption. This ability of antalarmin to reduce established ethanol consumption is apparently unrelated to changes in ingestive behaviour, or a generalised anxiolytic action. For these reasons, such drugs may provide a new therapeutic approach for the treatment of alcoholism; however, this requires further investigation.