fMRI response in the medial prefrontal cortex predicts cocaine but not sucrose self-administration history.
NeuroImage. 2012-09-01; 62(3): 1857-1866
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1. Neuroimage. 2012 Sep;62(3):1857-66. doi: 10.1016/j.neuroimage.2012.05.076. Epub
2012 Jun 1.
fMRI response in the medial prefrontal cortex predicts cocaine but not sucrose
Lu H(1), Chefer S, Kurup PK, Guillem K, Vaupel DB, Ross TJ, Moore A, Yang Y,
Peoples LL, Stein EA.
(1)Neuroimaging Research Branch, National Institute on Drug Abuse, National
Institutes of Health, Baltimore, MD 21224, USA.
Repeated cocaine exposure induces long-lasting neuroadaptations that alter
subsequent responsiveness to the drug. However, systems-level investigation of
these neuroplastic consequences is limited. We employed a rodent model of drug
addiction to investigate neuroadaptations associated with prolonged forced
abstinence after long-term cocaine self-administration (SA). Since natural
rewards also activate the mesolimbic reward system in a partially overlapping
fashion as cocaine, our design also included a sucrose SA group. Rats were
trained to self-administer cocaine or sucrose using a fixed-ratio one,
long-access schedule (6 h/day for 20 days). A third group of naïve, sedentary
rats served as a negative control. After 30 days of abstinence, the reactivity of
the reward system was assessed with functional magnetic resonance imaging (fMRI)
following an intravenous cocaine injection challenge. A strong positive fMRI
response, as measured by fractional cerebral blood volume changes relative to
baseline (CBV%), was seen in the sedentary control group in such cortico-limbic
regions as medial prefrontal cortex and anterior cingulate cortex. In contrast,
both the cocaine and sucrose SA groups demonstrated a very similar initial
negative fMRI response followed by an attenuated positive response. The magnitude
of the mPFC response was significantly correlated with the total amount of
reinforcer intake during the training sessions for the cocaine SA but not for the
sucrose SA group. Given that the two SA groups had identical histories of operant
training and handling, this region-specific group difference revealed by
regression analysis may reflect the development of neuroadaptive mechanisms
specifically related to the emergence of addiction-like behavior that occurs only
in cocaine SA animals.
Published by Elsevier Inc.
PMID: 22664568 [Indexed for MEDLINE]