Effects of an adenosine A2A receptor blockade in the nucleus accumbens on locomotion, feeding, and prepulse inhibition in rats.

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.