Effects of an adenosine A_2A 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 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.

Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus accumbens core attenuate the locomotor suppression induced by haloperidol in rats

“…Effect size analyses indicated that MSX-3 produced moderate-to-large effects when injected into nucleus accumbens core. These positive effects obtained with MSX-3 injections into the core clearly demonstrate that nucleus accumbens is an effective site for the stimulation of locomotion by MSX-3 in haloperidol-treated rats, an observation that is consistent with previous studies showing that adenosine A 2A receptors in nucleus accumbens are involved in the regulation of locomotion [6,7,31,59]. However, the robust and consistent effects observed after injections of MSX-3 into the nucleus accumbens core were not mimicked by injections into the dorsomedial shell.…”

“…In addition, doses of MSX-3 that reversed haloperidol-induced lever pressing had no effects when injected without the DA antagonist [23]. Although recent work has indicated that intra-accumbens injections of MSX-3 can increase locomotion [59], that paper used behavioral methods that were substantially different from those used in the present study (i.e., open-field activity in habituated animals). Moreover, previous studies showing that systemic injections of MSX-3 increased locomotion used younger rats than the present study [2,41,72].…”

“…The dose of haloperidol used (0.5 mg/kg), and the 14 day repeated administration procedures, were selected based upon previous studies [18,81]. The doses of MSX-3 were chosen based upon pilot experiments, as well as the results of previously published studies [30,59].…”

“…The adenosine A 2A agonist CGS 21680 was shown to suppress locomotion when injected directly into the nucleus accumbens [6,7,31]. Infusions of the adenosine A 2A antagonist MSX-3 directly into the nucleus accumbens produced a doserelated increase in locomotor activity [59]. Moreover, there is considerable evidence indicating that interference with DA transmission in nucleus accumbens leads to a suppression of spontaneous locomotion [5,16,19,46].…”

“…Nucleus accumbens was investigated because, as described above, this brain area is involved in the regulation of locomotor activity. Although previous studies have examined the effects of local nucleus accumbens injections of MSX-3 on locomotor activity [59], these studies did not differentiate between core and shell subregions, and did not assess the effects of A 2A antagonism in the presence of a DA antagonist. The VLS site was chosen as a control striatal site because this striatal subregion is thought to be involved in motor functions such as tremor [20,21,39,54,67,74] and skilled motor control [20,65,66], but is not thought to be important for locomotion [19,39,42].…”