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RATIONALE The prefrontal cortex is implicated in the pathophysiology of depression, and hypoactivity of this brain area has been found in depressed patients. Reduced function of the serotonergic and noradrenergic systems is another feature of depression. OBJECTIVES The present study was aimed at characterizing neurochemically and behaviorally the(More)
The effects of the repeated administration of milnacipran, a serotonin (5-HT)-noradrenaline reuptake inhibitor (SNRI), on the functional status of somatodendritic 5-HT1A receptors, and postsynaptic 5-HT1A receptors were explored using electrophysiological approaches in rats. In-vitro electrophysiological recordings in the dorsal raphe nucleus showed that(More)
Whether Rho-kinase activity is really associated with the pathogenesis of cerebral infarction remains unclear. To consider this question, we investigated correspondences between severity of neurological deficit, infarct size, amount of various marker proteins, and Rho-kinase activity in a rat cerebral infarction model. Sodium laurate was injected into the(More)
We investigated the neuroprotective effects of fasudil's active metabolite, hydroxyfasudil, a Rho-kinase inhibitor, in a rat stroke model in which endothelial damage and subsequent thrombotic occlusion were selectively induced in perforating arteries. By examining the effects on the endothelial damage/dysfunction, we thought to explore the mechanism of(More)
BACKGROUND Rho-kinase (ROCK) is a downstream effector of Rho GTPase that is known to regulate various pathological processes important to the development of ischemic stroke, such as thrombus formation, inflammation, and vasospasm. Inhibition of ROCK leads to decreased infarct size in animal models of ischemic stroke. This study tests the hypothesis that(More)
The aim of this study was to investigate the possible effects of the Rho-kinase inhibitor, fasudil, on the lysophosphatidic acid (LPA)-induced neurite retraction in N1E-115 cells. In cultured N1E-115 cells, LPA produced a marked increase in the population of rounded cells. Fasudil or hydroxyfasudil, an active metabolite of fasudil, blocked cell rounding in(More)
Rho kinase (ROCK), one of the serine/threonine kinases, is involved in pathologic conditions, and its activation causes neuronal cell death. Fasudil, a selective ROCK inhibitor, has been reported to cause increased cerebral blood flow (CBF) in the ischemic brain and protect against neuronal cell death by inhibiting ROCK. Ozagrel, a thromboxane A(2) synthase(More)
We investigated the anxiolytic effects and mechanism of action of a new anxiolytic drug, (R)-piperonyl-1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine-3- carboxamide hydrochloride (AP521). AP521 showed equal or more potent anxiolytic-like effects compared with diazepam, a benzodiazepine receptor agonist, or tandospirone, a partial 5-hydroxytryptamine(More)
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