Glutamate receptors represent the main excitatory receptors in synaptic transmission in the brain and have been intensively studied over the last 15 yr. Although clinical settings involving glutamate receptor modulators or antagonists usually involve stroke, acute brain injury, epilepsy, and neuropathic pain, both metabotropic and ionotropic classes of glutamate receptor also appear to play a role in addiction and cognition. For example, sensitization to cocaine upon chronic exposure to this stimulant appears to be mediated in part by Ca2+ influx through a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (1), and an mGluR2 agonist attenuates the disruptive effects of phencycli-dine on working memory (2). We will provide an overview of the molecular and physiological properties of glutamate receptors and review their subunit-specific pharmacology. As much as possible, we will focus on features of glutamate receptor activation and desensitization that may be most relevant to addiction and cognitive processing. More extensive information on glutamate receptor pharmacology can be found in the literature (3-5).
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