6,47,99-101 The NRHypo hypothesis Recent novel approaches to the treatment and prevention of drug-induced and idiopathic psychoses have emerged from the NMDA glutamate receptor hypofunction hypothesis.102-106 Simply stated, the hypothesis proposes that NRHypo, the condition induced in the human or animal brain by an NMDA antagonist drug, might also be viewed as a model for a disease mechanism which could explain the expression of psychosis, cognitive impairments, and certain neuropathological findings

in patients with neuropsychiatrie disorders like schizophrenia and AD. The disease mechanism itself might involve dysfunction of the NMDA receptor or downstream Inhibitors,research,lifescience,medical effects that can be modeled by blocking NMDA receptors. An important consequence of blocking NMDA Inhibitors,research,lifescience,medical receptors is excessive release of Glu107,108 and acetylcholine109-111 (ACh) in multiple brain regions. It, has been proposed that, this excessive release of excitatory transmitters and consequent, overstimulation of postsynaptic neurons might, explain the cognitive and behavioral disturbances associated with the NRHypo

state.100,107,108 Inhibitors,research,lifescience,medical It. is assumed that both genetic and nongenetic factors can contribute to the NRHypo state, and that NRHypo can interact with a variety of other disease mechanisms. Neurotoxic effects of NMDA glutamate receptor antagonists In order to better understand the mechanisms underlying the clinical effects of NMDA antagonist drugs and the clinical XL184 supplier consequences of an NRHypo state, several research groups have begun examining the consequences Inhibitors,research,lifescience,medical of drug-induced NRHypo and have shown that one typical consequence is excessive release of Glu107,108 and Ach109,111 in the cerebral cortex. Therefore, a concerted effort is being made to understand the mechanism by which NRHypo triggers excessive release of excitatory neurotransmitters in the hope that this may provide new insights into the pathophysiology of psychosis and certain cognitive impairments.

While moderately increased neurotransmitter release and associated overstimulation of postsynaptic Inhibitors,research,lifescience,medical neurons can produce certain cognitive and psychotic symptoms, unremittingly severe and chronic NRHypo and associated MycoClean Mycoplasma Removal Kit excitatory transmitter release can lead to neurodegenerative changes in the brain. For research purposes, creating a drug-induced NRHypo state in the rodent brain provides an excellent means of identifying neuronal populations that are at risk of being hyperstimulaled and potentially injured as a consequence of the NRHypo state. Described below, our findings indicate that a protracted NRHypo state can trigger neuronal injury throughout many corticolimbic brain regions.112,113 Presumably any of these hyperstimulated neurons can be instrumental in producing NMDA antagonist-induced psychotic symptoms or cognitive impairments.