Glutamate receptors in extinction and extinction-based therapies for psychiatric illness.
Some psychiatric illnesses involve a learned component. For example, in posttraumatic stress disorder, memories triggered by trauma-associated cues trigger fear and anxiety, and in addiction, drug-associated cues elicit drug craving and withdrawal. Clinical interventions to reduce the impact of conditioned cues in eliciting these maladaptive conditioned responses are likely to be beneficial. Extinction is a method of lessening conditioned responses and involves repeated exposures to a cue in the absence of the event it once predicted. We believe that an improved understanding of the behavioral and neurobiological mechanisms of extinction will allow extinction-like procedures in the clinic to become more effective. Research on the role of glutamate-the major excitatory neurotransmitter in the mammalian brain-in extinction has led to the development of pharmacotherapeutics to enhance the efficacy of extinction-based protocols in clinical populations. In this review, we describe what has been learned about glutamate actions at its three major receptor types (N-methyl-D-aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and metabotropic glutamate receptors) in the extinction of conditioned fear, drug craving, and withdrawal. We then discuss how these findings have been applied in clinical research.
Myers
Karyn M
KM
Behavioral Genetics Laboratory, McLean Hospital, Department of Psychiatry, Harvard Medical School, Belmont, MA 02478, USA. kmyers@mclean.harvard.edu
Carlezon
William A
WA
Davis
Michael
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018698:Glutamic Acid