Behavioral studies indicate that chronic food restriction enhances sensitivity to the rewarding and motor-activating effects of abused drugs. We and others have demonstrated a role for the D1 dopamine receptor (D1R) subtype among the several localized neuroadaptations that correlate with this increased sensitivity. Related evidence indicates that D1R-mediated activation of MAP kinase signaling may be a factor in the enhanced responses of drug-sensitive rats. Our objective is to determine whether there is a brain regional increase in MAP kinase signaling upon D1R activation in chronically food-restricted (FR) compared to ad libitum-fed (AL) rats.
The first aim i s to determine, by Western Blot and immunohistochemistry (IHC), if intracerebroventricular injection of a D1 agonist, SKF-82958, results in increased ERK1/2/MAP kinase phosphorylation in striatal regions of FR versus AL rats.
The second aim i s to determine by IHC whether a MAP/ERK kinase (MEK) inhibitor, PD98059, reverses the augmented SKF-82958-induced c-Fos expression otherwise seen in the striatum of FR versus AL rats.
The third aim i s to determine, by measuring photobeam interruption to count movements, whether PD98059 reverses the augmented SKF-82958-induced locomotor activity that is otherwise observed in FR compared to AL rats.
