The Journal of Neuroscience, April 1, 2001, 21(7):2526-2535
Limbic-Cortical-Ventral Striatal Activation during Retrieval of a
Discrete Cocaine-Associated Stimulus: A Cellular Imaging Study with 
Protein Kinase C Expression
Kerrie L.
Thomas and
Barry J.
Everitt
Department of Experimental Psychology, University of Cambridge,
Cambridge CB2 3EB, United Kingdom
We investigated the neuronal activation associated with reexposure
to a discrete cocaine-associated stimulus using in situ hybridization to quantify the expression of the plasticity-regulated gene, 
protein kinase C ( PKC), in the limbic-cortical-ventral striatal system. Groups of rats were trained to self-administer cocaine
paired with a light stimulus (Paired) or paired with an auditory
stimulus but also receiving light presentations yoked to those in the
Paired group (Unpaired). Additional groups received noncontingent
cocaine-light pairings (Pavlovian) or saline-light pairings (Saline)
that were yoked to the Paired group. After acquisition of
self-administration by the Paired and Unpaired groups, all groups had a
3 d drug- and training-free period before being reexposed to
noncontingent presentations of the light conditioning stimulus during a 5 min test session in the training context. There were four
major patterns of results for regional PKC expression 2 hr later.
(1) Changes occurred only in groups in which the light was predictive
of cocaine. (2) Increases were seen in the amygdala, but decreases were
seen in the medial prefrontal cortex. (3) No changes were seen in the
hippocampus. (4) Although changes were observed in the basal and
central nuclei of the amygdala and the prelimbic cortex in both the
Paired and Pavlovian groups, additional changes were observed in the
nucleus accumbens core, lateral amygdala, and anterior cingulate cortex
in the Pavlovian group. These results suggest not only that regionally
selective alterations in PKC expression are an index of the
retrieval of Pavlovian associations formed between a drug and a
discrete stimulus, but also that a distinct neural circuitry may
underlie Pavlovian stimulus-reward associations in cocaine-experienced rats.
Key words:
protein kinase C; cocaine; memory retrieval; nucleus
accumbens; frontal cortex; limbic system
Copyright © 2001 Society for Neuroscience 0270-6474/01/2172526-10$05.00/0
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