Astrocytes are crucial in contributing to the formation and maintenance of neural circuits and it is believed that disruption in this role can result in a number of neurodevelopmental disorders including schizophrenia. Evidence suggests that reduced numbers of astrocytes in deeper cortical layers are assocociated with a diminished expression of EAAT2, a glutamate transporter in astrocytes; supporting the glutamate hypothesis.Deficits in executive functions, such as planning, inhibition, and working memory, are pervasive in schizophrenia. Although these functions are separable, their dysfunction in schizophrenia may reflect an underlying deficit in the ability to represent goal related information in working memory, and to utilize this to direct cognition and behavior. These impairments have been linked to a number of neuroimaging and neuropathological abnormalities. For example, functional neuroimaging studies report evidence of reduced neural processing efficiency, whereby the dorsolateral prefrontal cortex is activated to a greater degree to achieve a certain level of performance relative to controls on working memory tasks. These abnormalities may be linked to the consistent post-mortem finding of reduced neuropil, evidenced by increased pyramidal cell density and reduced dendritic spine density. These cellular and functional abnormalities may also be reflected in structural neuroimaging studies that find reduced grey matter volume in association with deficits in working memory tasks.Positive symptoms have been linked to cortical thinning in the superior temporal gyrus. Severity of negative symptoms has been linked to reduced thickness in the left medial orbitofrontal cortex. Anhedonia, traditionally defined as a reduced capacity to experience pleasure, is frequently reported in schizophrenia.
Bretylium should be used only in an ICU or emergency department setting and should not be used elsewhere due to its dramatic actions and its predominant side effect of hypotension. Experimental uses
It is used in physiological and pharmacological research as an inhibitor of sympathetic transmission. Its mechanism of action is the inhibition of neurotransmitter release from sympathetic nerve terminals, both by the inhibition of action potentials in the nerve terminals and by other mechanisms. Its specificity for sympathetic nerves is achieved because it is a substrate for the noradrenaline transporter; hence, it accumulates inside nerve terminals which have this transporter. Synthesis

Quaternization of o-bromo-N,N-dimethylbenzylamine with ethyl-p-toluenesulfonate yields bretylium p-toluenesulfonate (tosylate). == References ==