However, here we show that staurosporine does not affect PDK1 phosphorylation of the endogenous PKM zeta in hippocampal slices. Thus, the biochemical in vitro effects of PKM zeta inhibitors correspond with their intracellular effects, and ZIP and chelerythrine, together with scrambled ZIP and staurosporine as controls, are effective tools to examine the function of PKM zeta in neurons.

This article is part of a Special Issue entitled ‘Cognitive Enhancers’. check details (C) 2012 Elsevier Ltd. All rights reserved.”
“Various experimental manipulations, usually

involving drug administration, have been used to produce symptoms of psychosis in healthy volunteers. Different drugs produce both common and distinct symptoms. A challenge is to understand how apparently different

manipulations can produce overlapping symptoms. We suggest that current Bayesian formulations of information processing in the brain provide a framework that maps onto neural circuitry and gives us a context within which we can relate the symptoms of psychosis to their underlying selleck chemicals causes. This helps us to understand the similarities and differences across the common models of psychosis.

The Bayesian approach emphasises processing of information in terms of both prior expectancies and current inputs. A mismatch between these leads us to update inferences about the world and to generate new predictions for the future. According to this model, what we experience shapes what we learn, and what we learn modifies how we experience things.

This simple idea gives us a powerful and flexible way of understanding the symptoms of psychosis where perception, learning and inference are deranged. We examine the predictions of the cognitive model in light of what we understand about the neuropharmacology of psychotomimetic drugs and thereby attempt to account for the common and the distinctive effects of NMDA receptor this website antagonists, serotonergic hallucinogens,

cannabinoids and dopamine agonists.

By acknowledging the importance of perception and perceptual aberration in mediating the positive symptoms of psychosis, the model also provides a useful setting in which to consider an under-researched model of psychosis-sensory deprivation.”
“Positive allosteric modulators of alpha-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket.