it indiscriminate increase of neurotransmitters due to drugs of abuse can degrade homeostatic physiologic mechanisms whereby neural networks change ICM and reestablish community synchrony. This could undermine MAP kinase inhibitor the compensatory ICM changes that restore exact timing of action potentials where ideal function depends. The resulting degradation in network function can secondarily contribute to the thought and cognitive deficits and mood disturbance inducing effects associated with these drugs of abuse. Another class of drugs of abuse, N methyl D-aspartic acid receptor antagonists such as phencyclidine and dizocilpine, will also be well known psychosis inducing compounds. In addition they activate GSK3B by reducing the phosphorylation/inhibition of Akt. Anticholinergic drugs could have similar deleterious clinical outcomes Lymph node by lowering cholinergic inhibition of GSK3. Thus, different classes of drugs of abuse, acting through different mechanisms yet sharing deleterious effects on cognition and thought and mood control, may discuss indiscriminate activation of GSK3 as an mechanism of action. However, drugs that prevent GSK3, such as for example 5HT2A receptor blockers and D2R, appear to have therapeutic effects in psychotic disorders whether secondary to drugs of abuse or as a result of mental disorders. 6. 0 Non Akt/GSK3 Mechanisms Associated with Myelination Given the difficulty, metabolic cost, and practical importance of myelination, the existence of parallel/redundant mechanisms to regulate myelination should not be unexpected. Such redundant signaling pathways substantially raise the complexity of phenotypes, but, they also be able to integrate/coordinate myelination Bosutinib clinical trial with all the metabolic and hormonal settings in addition to neuronal function. Hence, though focused on oligodendrocytes, this article isn’t meant to claim that oligodendrocytes are the only goal of successful treatments. It can however propose that the creation and preservation of myelin may be the weakest link of the human CNS and may represent a standard pathophysiology shared amongst multiple neuropsychiatric disorders. The differential involvement of myelin subtypes with different vulnerabilities may lead to different phenotypes despite sharing a common myelin substrate. This possibility is indirectly supported by the observation that many of the present treatment interventions have a wide spectral range of effectiveness and cover many illness categories as currently defined in the DSM. This wide spectral range of efficacy suggests that multiple pharmacologic as well as low pharmacologic treatments might act on a shared myelin vulnerability that, given the exceptionally extensive myelination of the human brain, manifests most distinctly in our species. The existence of a standard biological substrate may possibly also describe the complexity of phenotypes and frequent coexistence greater than one disorder inside the same individual.