Background
Prominent neurobiological theories of addiction posit a central role for aberrant
mesolimbic dopamine release but disagree as to whether repeated drug experience blunts
or enhances this system. Although drug withdrawal diminishes dopamine release, drug
sensitization augments mesolimbic function, and both processes have been linked to
drug seeking. One possibility is that the dopamine system can rapidly switch from
dampened to enhanced release depending on the specific drug-predictive environment.
To test this, we examined dopamine release when cues signaled delayed cocaine delivery
versus imminent cocaine self-administration.
Methods
Fast-scan cyclic voltammetry was used to examine real-time dopamine release while
simultaneously monitoring behavioral indexes of aversion as rats experienced a sweet
taste cue that predicted delayed cocaine availability and during self-administration.
Furthermore, the impact of cues signaling delayed drug availability on intracranial
self-stimulation, a broad measure of reward function, was assessed.
Results
We observed decreased mesolimbic dopamine concentrations, decreased reward sensitivity,
and negative affect in response to the cocaine-predictive taste cue that signaled
delayed cocaine availability. Importantly, dopamine concentration rapidly switched
to elevated levels to cues signaling imminent cocaine delivery in the subsequent self-administration
session.
Conclusions
These findings show rapid, bivalent contextual control over brain reward processing,
affect, and motivated behavior and have implications for mechanisms mediating substance
abuse.
Key Words
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Article info
Publication history
Published online: April 11, 2011
Accepted:
February 10,
2011
Received in revised form:
January 21,
2011
Received:
November 3,
2010
Identification
Copyright
© 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
