Lake Forest College1, Biology, Lake Forest, IL 60045 Rosalind Franklin University of Medicine and Science2, Cellular and Molecular Pharmacology, North Chicago, IL 60064 Kuei-Yuan.Tseng@rosalindfranklin.edu debburma@lakeforest.edu
FRONTAL CORTICAL ACTIVITY IS UPREGULATED AFTER THREE WEEKS WITHDRAWAL FROM REPEATED COCAINE EXPOSURE
In order to determine how repeated cocaine administration impacts the overall functional state of the mesocorticolimbic network, we assess cytochrome oxidase (CO-I) staining as a measure of metabolic activity. CO-I is used to reflect functional changes of the mesocorticolimbic network. We found a significant CO-I staining increase in the medial prefrontal cortex, orbitofrontal and cingulate cortices after three weeks, not three days withdrawal from repeated cocaine. Importantly, prefrontal CO-I upregulation seems to require longer than three days to develop, as a slight increase was found after three days withdrawal. Overall, the CO-I data revealed that synaptic-driven neuronal activity within the mesocorticolimic brain regions is upregulated in rats exposed to cocaine. Based on these results, the following can be interpreted. A higher energy demand may be required to sustain basal prefrontal function, which in turn may lead to a hyper-reactive frontal cortical state after three weeks withdrawal. If this is the case, increasing the mesocortical input demand would fail to further increase metabolic responses in the cocaine group. A metabolic failure to match a higher mesocortical demand would be indicative of a reduced functional capacity of the frontal cortices, which could lead to behavioral deficits in cocaine treated animals.
[Abstract (DOC)]