title: The role of nucleus accumbens adenosine-opioid interaction in mediating palatable food intake.
abstract: Nucleus accumbens micro-opioid stimulation leads to robust increases in the intake of highly palatable foods, such as a high-fat diet. While interactions between opioids and certain striatal neurotransmitters underlying this phenomenon have been explored, many potential interactions have not. Striatal adenosine has been shown to have a significant influence on striatal neurotransmission and locomotor activity behavior, however the interaction between opioids and adenosine on feeding behaviors has received less attention. The present study explored this interaction within the context of opioid-driven consumption of a high-fat diet. Specifically, intra-accumbens administration of selective A1 and A2(A) adenosine receptor ligands, with or without concurrent administration of the micro-opioid agonist (D)-Ala(2),N,Me-Phe(4),Gly-ol(5)-enkaphalin (DAMGO), on high-fat consumption and associated locomotor activity was examined. The A1 receptor agonist 2-Chloro-N6-cyclopentyladenosine (CCPA) had no effect on either baseline or DAMGO-induced locomotor or consumption behaviors associated with the high-fat diet. However, the A2(A) receptor agonist 2-p-(2 carboxyethyl)-phenethylamino-5'-N-ethylcarboxamido adenosine hydrochloride (CGS 21680) and the prodrug of the A2(A) receptor antagonist MSX-2, 3-(3-hydroxypropyl)-8-(m-methoxystyryl)-7-methyl-1-propargylxanthine phosphate disodium salt (MSX-3) produced the expected decrease and increase in locomotor activity, respectively. CGS 21680 had no effect on baseline or DAMGO-driven consumption of the high-fat diet. MSX-3 had no effect on DAMGO-induced locomotor activity but increased DAMGO-induced consumption. Lastly, the increased activity and consumption produced by MSX-3 alone was blocked by prior administration of the opioid antagonist naltrexone. In summary, these results suggest a potential role of striatal adenosine A2(A) receptors in mediating baseline and striatal opioid-mediated intake of a high-fat diet.
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, PA 17033, USA.
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Pritchett
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Pardee
authors.forename: Sophia R
authors.initials: SR
authors.lastname: McGuirk
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Will
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002404:Catheterization; D002491:Central Nervous System Agents / Q000494:pharmacology; D004041:Dietary Fats; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010627:Phenethylamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D002491:Central Nervous System Agents; D004041:Dietary Fats; C113602:MSX 3 compound; D009292:Narcotic Antagonists; D010627:Phenethylamines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D017450:Receptors, Opioid, mu; D014970:Xanthines; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C058394:2-chloro-N(6)cyclopentyladenosine; D009271:Naltrexone; D000241:Adenosine