AMPA receptor synaptic plasticity induced by psychostimulants: the past, present, and therapeutic future.
Experience-dependent plasticity at excitatory synapses of the mesocorticolimbic system is a fundamental brain mechanism that enables adaptation to an ever-changing environment. These synaptic responses are critical for the planning and execution of adaptive behaviors that maximize survival. The mesocorticolimbic system mediates procurement of positive reinforcers such as food and sex; however, drugs of abuse resculpt this crucial circuitry to promote compulsive drug-seeking behavior. This review will discuss the long-term changes in glutamatergic neurotransmission that occur within the mesolimbic system following cocaine exposure. In addition, we will examine how these long-lasting neuroadaptations may drive the pathology of psychostimulant addiction. Finally, we review clinical trials that highlight antagonists at excitatory AMPA receptors as promising targets against cocaine abuse.
Bowers
M Scott
MS
Virginia Institute for Psychiatric and Behavioral Genetics, VCU Psychiatry, Richmond, VA 23284, USA.
Chen
Billy T
BT
Bonci
Antonello
A
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D003042:Cocaine