title: Stimulation of adenosine receptors in the nucleus accumbens reverses the expression of cocaine sensitization and cross-sensitization to dopamine D2 receptors in rats.
abstract: Adenosine receptors co-localize with dopamine receptors on medium spiny nucleus accumbens (NAc) neurons where they antagonize dopamine receptor activity. It remains unclear whether adenosine receptor stimulation in the NAc restores cocaine-induced enhancements in dopamine receptor sensitivity. The goal of these studies was to determine whether stimulating A(1) or A(2A) receptors in the NAc reduces the expression of cocaine sensitization. Rats were sensitized with 7 daily treatments of cocaine (15 mg/kg, i.p.). Following one-week withdrawal, the effects of intra-NAc microinjections of the adenosine kinase inhibitor (ABT-702), the adenosine deaminase inhibitor (deoxycoformycin; DCF), the specific A(1) receptor agonist (CPA) and the specific A(2A) receptor agonist (CGS 21680) were tested on the behavioral expression of cocaine sensitization. The results indicate that intra-NAc pretreatment of ABT-702 and DCF dose-dependently blocked the expression of cocaine sensitization while having no effects on acute cocaine sensitivity, suggesting that upregulation of endogenous adenosine in the accumbens is sufficient to non-selectively stimulate adenosine receptors and reverse the expression of cocaine sensitization. Intra-NAc treatment of CPA significantly inhibited the expression of cocaine sensitization, which was reversed by both A(1) and A(2A) receptor antagonism. Intra-NAc treatment of CGS 21680 also significantly inhibited the expression of cocaine sensitization, which was selectively reversed by A(2A), but not A(1), receptor antagonism. Finally, CGS 21680 also inhibited the expression of quinpirole cross-sensitization. Together, these findings suggest that adenosine receptor stimulation in the NAc is sufficient to reverse the behavioral expression of cocaine sensitization and that A(2A) receptors blunt cocaine-induced sensitization of postsynaptic D(2) receptors.
authors: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, USA.
authors: Benjamin D
authors: BD
authors: Hobson
authors: Kathryn E
authors: KE
authors: Merritt
authors: Ryan K
authors: RK
authors: Bachtell
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology; D000248:Adenosine Kinase / Q000378:metabolism; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009025:Morpholines / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058892:Adenosine Deaminase Inhibitors; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D009025:Morpholines; D010627:Phenethylamines; D011743:Pyrimidines; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D018047:Receptors, Purinergic P1; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019257:Quinpirole; C416933:ABT 702; D000248:Adenosine Kinase; D000243:Adenosine Deaminase; D003042:Cocaine; D000241:Adenosine