P.3.c.077 Evaluation of the effectiveness and effect on cognitive functioning of aripiprazole in a range of schizophrenia patients

Abstract

This chapter focuses on GPCR (dopaminergic, cholinergic, and metabotropic glutamatergic) and receptor tyrosine kinase (PDGF and insulin) regulation of NMDA channel activity and NMDA-mediated neurotransmission. The N-methyl-D -aspartate receptor (NMDAR) is a ligand-gated ion channel that belongs to a complex of proteins (enzymes, receptors, scaffolding proteins) that has recently been termed the NMDAR complex (NRC). The NRC is situated at postsynaptic sites in the CNS and is strategically located to regulate excitatory neurotransmission. The mechanisms by which NMDARs are modulated by signaling molecules and signal transduction cascades is of particular importance to understanding excitatory synaptic transmission and synaptic plasticity. In addition, several neurological disorders, for example, schizophrenia, epilepsy, Parkinson disease, and ischemia/stroke, are associated with an imbalance in NMDAR activity. Recent evidence demonstrates that modulation of NMDAR currents is a dynamic process that requires the interaction of several kinases, phosphatases, and intracellular calcium. The interplay of these molecular molecules is largely receptor- and cell-type specific and is likely to account for changes in synaptic transmission and the onset of synaptic plasticity. It is becoming clear that intracellular signaling molecules work in concert with other kinases, phosphatases, scaffolding proteins, and intracellular calcium. Biochemical studies have revealed that the NRC is a multiprotein complex that places kinases and phosphatases in strategic locations such that they are able to module excitatory neurotransmission.