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J Neuropsychiatry Clin Neurosci 1997; 9:482-497
Copyright © 1997 by American Neuropsychiatric Association
The neurobiology of drug addiction
GF Koob and EJ Nestler
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Animals models have begun to provide insights into the neurobiological
basis of reinforcement in drug addiction. The reinforcing effects of
indirect sympathomimetics such as cocaine and amphetamine appear to depend
on release of dopamine in the terminal fields of the mesocorticolimbic
dopamine system. The acute reinforcing effects of opiates involve not only
an activation of dopamine, but also dopamine- independent elements in the
terminal regions of the mesocorticolimbic dopamine system. Nicotine's
reinforcing effects may involve both dopaminergic and opioid peptidergic
systems. Ethanol's reinforcing effects may result from multiple
neurotransmitter interactions including gamma-aminobutyric acid, glutamate,
dopamine, opioid peptides, and serotonin. Subtle changes in neurochemical
function and signal transduction and transcription mechanisms in sensitive
neuronal elements in the extended amygdala may be mediators of chronic drug
action that lead to vulnerability to relapse and may provide exciting
insight into the neuroadaptations associated with drug addiction.
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