Intra-nacc adenosine and its role in mediating palatable food intake: interactions with striatal opioids

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Striatal adenosine is believed to have a significant modulatory role over a variety of striatal circuitry and associated psychomotor and feeding behaviors. However, it is currently unknown to what extent striatal adenosine receptors differently contribute to the extensively studied nucleus accumbens opiate-induced feeding behavior. The present study investigated the intra-NAcc effects of selective A1 and A2A adenosine receptor ligands alone and when co-administered with the [mu]-opioid agonist DAMGO or the opiate antagonist naltrexone. The influence of the A1 receptor agonist CCPA, the A1 receptor antagonist DPX, the A2A receptor agonist CGS 21680, and the A2A receptor antagonist MSX-3 on feeding behaviors was investigated. CCPA had no effect on baseline or DAMGO-induced feeding or activity, while CGS 21680 decreased baseline activity but had no effect on feeding. DPX decreased feeding alone, while having no effect on activity. MSX-3 produced both robust feeding and activity increases and facilitated DAMGO-induced behaviors. These effects were blocked by naltrexone. Overall, it was observed that manipulation of A2A receptors produced stronger modulatory effects than A1 receptor manipulation on consumption, both alone and when co-administered with DAMGO. Indeed, it is expected that A2A receptors, being more densely localized throughout the accumbens, would have a greater impact on behaviors mediated by the nucleus accumbens than A1 receptors. In summary, these results suggest an intriguing role for striatal adenosine in mediating baseline and striatal opioid-mediated behaviors.