Though GABA(A)R-mediated transmission is required for generation of SWRs little is known about the possible implication of different subtypes of GABA(A)R in SWRs. One of the most abundant subtypes of GABA(A) receptor in the hippocampus contains the alpha 5 subunit. This subtype is specifically located on pyramidal

cells preferably mediating tonic inhibition and is implicated Ro 61-8048 price in memory processes. Using hippocampal slices of adult rats we investigated the effects of etomidate and L-655,708, two substances that display opposite effects on the alpha 5 subunit-containing GABA(A) receptor (alpha 5GABA(A)R), in the generation of spontaneous SWRs. We found that the two drugs at concentrations assumed to display preferential interaction with the alpha 5GABA(A)Rs had opposite effects on: a) the probability of generation of SWRs in episodes of multiple consecutive events (i.e. clusters), b) the timing of generation of consecutive events

in clusters, c) the strength of ripple oscillation and d) the ability of the network to initiate episodes of SWRs. Most of the opposite drug effects on SWRs were also observed at higher concentrations. The present finding demonstrates a crucial involvement of the alpha 5GABA(A)Rs in the SWR activity suggesting that distinct facets of the GABA(A)R-mediated transmission are implicated in particular features of the SWRs activity. In addition, the present results are consistent with the known opposite effects of the two drugs on memory

performance. (C) 2010 Elsevier Ltd. All rights reserved.”
“Cannabinoids (CBs) are implicated in a number of physiological and pathological mechanisms in C59 wnt ic50 the central nervous system, but their exact role in post-ischemic brain injury is unclear. The toxic and neuroprotective effects of synthetic and endogenous CBs were evaluated in rat organotypic hippocampal slices exposed to 20 min oxygen glucose deprivation (OGD) and in gerbils subjected to bilateral carotid occlusion for 5 min. When present in the incubation medium, the synthetic CB agonists WIN 55212-2 and CP 55940 (1-30 mu M) and the CBI agonist ACEA exacerbated CA1 injury induced by OGD, whereas the CBI receptor antagonists AM 251 and LY 320135 were neuroprotective SU5402 price with maximal activity at 1 mu M. AM 251 (at 3 mg/kg, i.p.) also attenuated CM pyramidal cell death in gerbils in vivo. The endocannabinoid 2-arachidonoylglycerol (2-AG) reduced OGD injury in hippocampal slices at 0.1-1 mu M, whereas anandamide (AEA) was neurotoxic at the same concentrations. The effects of WIN 55212-2, AEA and 2-AG in slices were all dependent on the activation of CB1 but not CB2 receptors, except for the toxic effects of AEA that were also dependent on vanilloid TRPV1 receptors. Our results suggest that exogenous administration of CB1 agonists and the production of endocannabinoids “”on demand”" may produce different, if not opposite, effects on the fate of neurons following cerebral ischemia.