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Journal of Neuroscience, Vol 12, 4112-4121, Copyright © 1992 by Society for Neuroscience
Evidence for conditional neuronal activation following exposure to a cocaine-paired environment: role of forebrain limbic structures
EE Brown, GS Robertson and HC Fibiger
Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
The reinforcing properties of cocaine can readily become associated with
salient environmental stimuli that acquire secondary reinforcing
properties. This form of classical conditioning is of considerable clinical
relevance as intense craving can be evoked by the presentation of stimuli
previously associated with the effects of cocaine. To understand better the
neurobiology of cocaine-induced environment- specific conditioning, Fos
expression was examined in the forebrain of rats exposed to an environment
in which they had previously received cocaine. These results were compared
to those observed following an acute injection of cocaine. Consistent with
its stimulant actions, cocaine produced an increase in locomotion that was
accompanied by an increase in Fos expression within specific limbic regions
(cingulate cortex, claustrum, piriform cortex, lateral septal nucleus,
paraventricular nucleus of the thalamus, lateral habenula, and amygdala) as
well as the basal ganglia (dorsomedial striatum and nucleus accumbens).
Exposure of rats to the cocaine-paired environment also produced an
increase in locomotion, as compared to various control groups. In addition
to this behavioral effect, conditioned subjects exhibited a significant
increase in Fos expression within the cingulate cortex, claustrum, lateral
septal nucleus, paraventricular nucleus of the thalamus, lateral habenula,
and the amygdala, suggesting increased neuronal activity within these
regions. In contrast to the dramatic effects observed within these
structures, no conditional activation was observed within the piriform
cortex, nucleus accumbens, or dorsal striatum, suggesting that these brain
areas are not involved in the conditioned response. The present findings
indicate that specific limbic regions exhibit increased neuronal activation
during the presentation of cocaine-paired cues and may be involved in the
formation of associations between cocaine's stimulant actions and the
environment in which the drug administration occurred. Although the nucleus
accumbens is necessary for the reinforcing and locomotor effects of
cocaine, it does not exhibit a conditional Fos response, suggesting that
different neural circuits are involved in the unconditioned and conditioned
effects of cocaine.
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