Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Animals
-
Central Nervous System Stimulants / pharmacology*
-
Clinical Trials as Topic
-
Cocaine / pharmacology*
-
Cocaine-Related Disorders / drug therapy
-
Cocaine-Related Disorders / physiopathology
-
Excitatory Amino Acid Antagonists / pharmacology
-
Excitatory Amino Acid Antagonists / therapeutic use
-
Glutamic Acid / metabolism
-
Humans
-
Limbic System / drug effects
-
Limbic System / metabolism
-
Limbic System / physiology
-
Models, Biological
-
Neuronal Plasticity / drug effects*
-
Prefrontal Cortex / drug effects
-
Prefrontal Cortex / metabolism
-
Prefrontal Cortex / physiology
-
Receptors, AMPA / physiology*
-
Signal Transduction / drug effects
-
Signal Transduction / physiology
-
Synapses / drug effects*
-
Synaptic Transmission / drug effects
Substances
-
Central Nervous System Stimulants
-
Excitatory Amino Acid Antagonists
-
Receptors, AMPA
-
Glutamic Acid
-
Cocaine