Drugs that Target the Glutamate Synapse: Implications for the Glutamate Hypothesis of Schizophrenia
This chapter describes a brief history and the recent evolution of the glutamate hypothesis of schizophrenia: from its divergence with the dopamine hypothesis to its implication in the widespread cortical and subcortical dysfunction found in schizophrenia. It also describes some of the working hypotheses about the integration of glutamate, along with other neurotransmitter systems, in the more generalized etiology of the disease, ultimately better clarifying the pathophysiology and conceivable therapeutic pharmacology of schizophrenia. Pertinent animal models of the disease state are highlighted to showcase some of the tools used in the development and verification of new pharmacological treatments that target the glutamate synapse, either through a direct or indirect improvement of glutamatergic signalling. The chapter concludes with a discussion of new potential therapeutic targets and strategies to improve neuronal function at the glutamate synapse.