Transgenic mice lacking IL-2 are susceptible to autoimmune diseases. Cytokines can influence the activity of the glutamate system.9 The glutamate system is closely connected to dopaminergic and serotonergic neurons. Hypofunction of the N-methyl-D-aspartate (NMDA) receptor leads to increased dopaminergic activity in the frontal cortex. The NMDA glutamate hypothesis
offers a possible link between the various theories surrounding Inhibitors,research,lifescience,medical the immune system and the hypothesis related to neurotransmitters. The growing importance of amino acid transmitters like glutamate was recognized from neuroimaging studies and neuro-pathological findings showing an involvement of the cerebral cortex (in which the major neurons are glutamatergic) in the neuropathology of Inhibitors,research,lifescience,medical schizophrenia. Further support came from the psychotomimetic effects of the NMDA-receptor antagonists phenylcyclidine (PCP), dizocilpine (MK-801), and ketamine. The theories focused on these NMDA receptors because of the psychomimetic effects of NMDA antagonists. Most notably, PCP and ketamine can induce symptoms related to schizophrenic symptomatology in healthy human subjects. Positive symptoms like grandiose paranoid delusions, bizarre ideation, and hallucinations have been described, as have negative symptoms like blunted
affect and psychomotor retardation. Furthermore, cognitive Inhibitors,research,lifescience,medical deficits related to circuits in the frontal cortex have been
observed, like distractibility, reduced verbal fluency, and working memory deficits. Cognitive deficits related to temporal hippocampal circuits have also been reported, like the disruption of new learning and reduced prepulse inhibition Inhibitors,research,lifescience,medical of the startle response. In the so-called revised dopamine Inhibitors,research,lifescience,medical hypothesis, Carlsson underlined the central role of glutamate-γ-aminobutyric acid (GARA) in neuronal circuits, which are closely connected to other neurotransmitters, eg, dopamine, norepinephrine, serotonin, acetylcholine, and glycine. The glutamate receptor system offers multiple targets for pathogenesis and pathophysiology in schizophrenia, and is rather complex. Four classes of glutamate receptors, the NMDA, the amino-3-hydroxy-5-methyl-4-isoxazolc propionic acid Adenosine (AMPA), the kainate, and the metabotropic receptors, each of which has a wide variety of subunits, form various receptor combinations, and can be learn more differentiated on this basis (Figure 2).10 These NM.DA antagonistic drugs lead to NMDA receptor hypofunction, which is due to the connections with the other neurotransmitter systems, producing an excessive release of excitatory transmitters in the cerebral cortex, and with other transmitters like dopamine. It is of interest that these psychotomimetic effects arc only seen in adults, and not in children or young adolescents.