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

Abstract

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 A2A 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 μg and 5 μg in 1 μl per side) of the selective A2A receptor antagonist MSX-2 or vehicle (1 μl per side) were administered into the NAc. Results show that blockade of intra-NAc adenosine A2A receptors by a high (5 μg), but not by a low (3 μg), 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 μg, but not 3 μg, MSX-3. These findings suggest that locomotor activity as well as intact PPI and feeding behavior rely on tonic activation of intra-NAc A2A receptors. The data add further support to the view that adenosine is a tonically active modulator of striatal function through actions on A2A receptors. © 2003 Wiley-Liss, Inc.