ERK Signaling in Food-Restricted, Drug-Sensitive Rats

New York University School Of Medicine, New York NY

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Abstract

DESCRIPTION (provided by applicant): 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 is 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 is 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 is 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.