These activations

were prevented by blocking mGluR2/3 with LY341459, an mGluR2/3 antagonist. Furthermore, selleck chemicals blocking ERK, PI3K and NFκB signaling pathways with U0126, LY294002 and pyrrolidine dithiocarbamate, respectively, significantly inhibited the mGluR2/3-mediated restorative effects. These results suggest that application of mGluR2/3 agonists after OGD insult can effectively reverse the OGD-reduced expression of GLAST proteins and restore clearance of extracellular glutamate by serially activating ERK/PI3K/NFκB signaling pathways in cultured astrocytes. “
“The learning and memory deficits associated with non-pathological ageing mainly result from alterations to the plasticity of neuronal network dynamics within the hippocampus. In addition to the broad spectrum of changes that affect the morphology and function of hippocampal excitatory circuits in the ageing brain, the impaired activation of the N-methyl-d-aspartate subtype of glutamate receptors (NMDA-R)

is a typical feature, altering the induction and maintenance of long-term potentiation, a major form of synaptic plasticity. In addition to glutamate, Transmembrane Transporters modulator the binding of a co-agonist at the strychnine-insensitive glycine-binding site is required for NMDA-R activation. This review presents recent evidence that: (i) the amino acid d-serine is an endogenous co-agonist of synaptic NMDA-R and necessary for long-term potentiation expression, (ii) reduced d-serine levels in the hippocampus contribute to synaptic plasticity and memory deficits in normal ageing, and Coproporphyrinogen III oxidase (iii) age-related oxidative stress selectively targets hippocampal serine racemase to impact d-serine availability in neuronal networks. These results emphasize the critical role of the hippocampal

d-serine-dependent pathway in changes affecting neuronal network dynamics in physiological ageing that underlie memory deficits. In addition, the central role of serine racemase in these changes opens new perspectives in the search for relevant therapeutic strategies aimed at reducing age-related memory defects. “
“There is great interest in outlining biological factors and behavioral characteristics that either predispose or predict vulnerability to substance use disorders. Response to an inescapable novel environment has been shown to predict a “drug-use-prone” phenotype that is defined by rapid acquisition of cocaine self-administration. Here, we showed that response to novelty can also predict the neurochemical and behavioral effects of acute and repeated cocaine in rats. We used cocaine self-administration under a fixed-ratio 1 schedule followed by fast-scan cyclic voltammetry in brain slices to measure subsecond dopamine (DA) release and uptake parameters in drug-use-prone and -resistant phenotypes.