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The Journal of Neuroscience, April 15, 2003, 23(8):3531
Prefrontal Glutamate Release into the Core of the Nucleus
Accumbens Mediates Cocaine-Induced Reinstatement of Drug-Seeking
Behavior
Krista
McFarland,
Christopher C.
Lapish, and
Peter W.
Kalivas
Department of Physiology ad Neuroscience, Medical University of
South Carolina, Charleston, South Carolina 29425
The relative contributions of glutamate and dopamine within the
nucleus accumbens to cocaine-induced reinstatement of drug-seeking behavior were assessed. When extinguished cocaine self-administration behavior was reinstated by a cocaine-priming injection, extracellular levels of both dopamine and glutamate were elevated in the nucleus accumbens. However, when yoked cocaine or saline control subjects were
administered a cocaine prime, only dopamine levels were elevated. Thus,
glutamate increased only when animals reinstated lever pressing, whereas dopamine increased regardless of behavior. The increase in
glutamate was not accounted for simply by the act of lever pressing
itself, because the cocaine self-administration group still
demonstrated elevated glutamate when the levers were withdrawn from the
operant chamber. Moreover, reinstatement of lever pressing for food did
not elevate extracellular glutamate, indicating that increased
glutamate initiated responding selectively for a drug reinforcement.
The source of glutamate was shown to be glutamatergic afferents from
the prefrontal cortex because inhibiting prefrontal cortical
glutamatergic neurons that project to the accumbens prevented the rise
in glutamate. Together, these data demonstrate that activation of a
glutamatergic projection from the prefrontal cortex to the nucleus
accumbens underlies cocaine-primed reinstatement of drug-seeking behavior.
Key words:
dopamine; glutamate; reinstatement; nucleus
accumbens; medial prefrontal cortex; self-administration; cocaine
Copyright © 2003 Society for Neuroscience 0270-6474/03/2383531-07$05.00/0
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