Glutamate is the principal excitatory transmitter in the mammalian CNS. A discussion of the role of glutamatergic transmission is included in this overview based on an extensive preclinical literature linking modulation of both ionotropic (N-methyl-D-aspartate) and metabotropic (mGluR2) glutamate receptor subtypes (Figure 12.3) to anxiety (Skolnick, 2000). Further, a recent, albeit preliminary, clinical study(Levine et al., 2001) appears to validate preclinical findings indicating that glutamate receptors are a valid target for the
development of novel anxiolytics. Like serotonin receptors, the glutamate receptor superfamily includes both ionotropic and G-protein coupled receptors (GPCR). The structural and molecular details of both receptor classes have been reviewed in detail (Schoepp, 2001; Conn and Pin, 1997; Palfreyman et al., 1994; Cotman et al., 1995). A brief overview of two glutamate receptor subtypes is provided as a background to place preclinical and clinical findings in context.