Brain research
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Orexinergic projections originating from the lateral hypothalamus (LH) have an important role in the acquisition of the LH-stimulation conditioned place preference (CPP). Among the brain areas associated with reward processing, LH orexinergic neurons send projections to the dentate gyrus (DG) region of the hippocampus, and it has been shown that orexin receptors are expressed in the DG. In this study, we investigated the role of intra-DG orexin-1 (OX1) and orexin-2 (OX2) receptors on acquisition, expression and extinction of CPP induced by stimulation of the LH. ⋯ In addition, these antagonists decreased the expression of LH-induced CPP. Moreover, OX1r but not OX2r antagonist could shorten the extinction duration of place preference. We conclude that the orexinergic projections from the LH to DG are involved in the development, expression and extinction of CPP induced by LH stimulation.
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Several neurological and psychiatric disorders present hyperexcitability of neurons in specific regions of the brain or spinal cord, partly because of some loss and/or dysfunction of gamma-amino butyric acid positive (GABA-ergic) inhibitory interneurons. Strategies that enhance inhibitory neurotransmission in the affected brain regions may therefore ease several or most deficits linked to these disorders. This perception has incited a huge interest in testing the efficacy of GABA-ergic interneuron cell grafting into regions of the brain or spinal cord exhibiting hyperexcitability, dearth of GABA-ergic interneurons or impaired inhibitory neurotransmission, using preclinical models of neurological and psychiatric disorders. ⋯ Moreover, future studies that are essential prior to considering the possible clinical application of these cells for the above neurological conditions are proposed. Particularly, the need for grafting studies utilizing medial ganglionic eminence-like progenitors generated from human pluripotent stem cells via directed differentiation approaches or somatic cells through direct reprogramming methods are emphasized. This article is part of a Special Issue entitled SI: PSC and the brain.
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While several morphometric studies have postulated a critical contribution of the cingulate cortex (CC) to the pathophysiology of schizophrenia based on abnormalities in CC volume, other studies have been inconclusive. Most such studies have focused only on changes in cortical volume, whereas other morphometric parameters such as surface area and cortical thickness could be more relevant and possibly account for these discrepancies. Furthermore, factors such as antipsychotic drug use and treatment duration may also influence cortical morphology. ⋯ No significant correlations were observed between CC volume and clinical variables. The results suggest that abnormalities in the CC as manifested by reduced surface area may contribute to cognitive dysfunction in schizophrenia. This article is part of a Special Issue entitled SI: PSC and the brain.
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The role of P2X2/3, P2X3, P2X4 or P2X7 and P2Y2, P2Y6, and P2Y12 receptors in neuropathic pain has been widely studied. In contrast, the role of P2Y1 receptors is scarcely studied. In this study we assessed the role of P2Y1 receptors in several neuropathic pain models in the rat. ⋯ Intrathecal injection of MRS2500 lost most of the antiallodynic effect when injected 14 days after injury. At this time, MRS2500 did not modify nerve-injury-induced P2Y1 receptors up-regulation. Our results suggest that P2Y1 receptors are localized in DRG, are up-regulated by nerve injury and play a pronociceptive role in development and, to a lesser extent, maintenance of neuropathic pain.
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Dopamine plays an important role in regulating neuronal functions in the central nervous system by activating the specific G-protein coupled receptors. Both D1 and D2 dopamine receptors are extensively distributed in the retinal neurons. In the present study, we investigated the effects of D1 receptor signaling on outward K(+) currents in acutely isolated rat retinal ganglion cells (RGCs) by patch-clamp techniques. ⋯ Both protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII) signaling pathways were likely involved in the SKF81297-induced suppression of the K(+) currents since either Rp-cAMP (10 μM), a cAMP/PKA signaling inhibitor, or KN-93 (10 μM), a specific CaMKII inhibitor, eliminated the SKF81297 effect. In contrast, neither protein kinase C (PKC) nor mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway seemed likely to be involved because both the PKC inhibitor bisindolylmaleimide IV (Bis IV) (10 μM) and the MAPK/ERK1/2 inhibitor U0126 (10 μM) did not block the SKF81297-induced suppression of the K(+) currents. These results suggest that activation of D1 receptors suppresses the Gb- and 4-AP-sensitive K(+) current components in rat RGCs through the intracellular PKA and CaMKII signaling pathways, thus modulating the RGC excitability.