The nucleus accumbens (NAc) subserves behaviors governed by natural rewards, i.e., feeding or exploration, and has been implicated in control of prepulse inhibition (PPI), a measure of sensorimotor gating. The present study sought to determine whether a tonic stimulation of adenosine A(2A) receptors in the rat NAc is involved in control of spontaneous locomotor activity, feeding behavior, and PPI. To this end, bilateral microinfusions of a prodrug (MSX-3) (3 microg and 5 microg in 1 microl per side) of the selective A(2A) receptor antagonist MSX-2 or vehicle (1 microl per side) were administered into the NAc. Results show that blockade of intra-NAc adenosine A(2A) receptors by a high (5 microg), but not by a low (3 microg), dose of MSX-3 increased locomotor activity in an open field, reduced food intake, and delayed intake onset in food-deprived rats examined in a test cage with standard laboratory chow. Furthermore, PPI was significantly disrupted after intra-NAc infusion of 5 microg, but not 3 microg, MSX-3. These findings suggest that locomotor activity as well as intact PPI and feeding behavior rely on tonic activation of intra-NAc A(2A) receptors. The data add further support to the view that adenosine is a tonically active modulator of striatal function through actions on A(2A) receptors.
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