title: Persistent reduction of cocaine seeking by pharmacological manipulation of adenosine A1 and A 2A receptors during extinction training in rats.
abstract: BACKGROUND
  Adenosine receptor stimulation and blockade have been shown to modulate a variety of cocaine-related behaviors.
  
  
  OBJECTIVE
  These studies identify the direct effects of adenosine receptor stimulation on cocaine seeking during extinction training and the persistent effects on subsequent reinstatement to cocaine seeking.
  
  
  METHODS
  Rats self-administered cocaine on a fixed ratio one schedule in daily sessions over 3 weeks. Following a 1-week withdrawal, the direct effects of adenosine receptor modulation were tested by administering the adenosine A1 receptor agonist, N(6)-cyclopentyladenosine (CPA, 0.03 and 0.1 mg/kg), the adenosine A2A agonist, CGS 21680 (0.03 and 0.1 mg/kg), the presynaptic adenosine A2A receptor antagonist, SCH 442416 (0.3, 1, and 3 mg/kg), or vehicle prior to each of six daily extinction sessions. The persistent effects of adenosine receptor modulation during extinction training were subsequently tested on reinstatement to cocaine seeking induced by cues, cocaine, and the dopamine D2 receptor agonist, quinpirole.
  
  
  RESULTS
  All doses of CPA and CGS 21680 impaired initial extinction responding; however, only CPA treatment during extinction produced persistent impairment in subsequent cocaine- and quinpirole-induced seeking. Dissociating CPA treatment from extinction did not alter extinction responding or subsequent reinstatement. Administration of SCH 442416 had no direct effects on extinction responding but produced dose-dependent persistent impairment of cocaine- and quinpirole-induced seeking.
  
  
  CONCLUSIONS
  These findings demonstrate that adenosine A1 or A2A receptor stimulation directly impair extinction responding. Interestingly, adenosine A1 receptor stimulation or presynaptic adenosine A2A receptor blockade during extinction produces lasting changes in relapse susceptibility.
authors.affiliation: Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado, UCB 345, Boulder, CO, 80309-0345, USA.
authors.forename: Casey E
authors.initials: CE
authors.lastname: O'Neill
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hobson
authors.forename: Sophia C
authors.initials: SC
authors.lastname: Levis
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Bachtell
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D019970:Cocaine-Related Disorders / Q000523:psychology*; D003463:Cues; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000187:drug effects*; D043705:Receptor, Adenosine A2A / Q000187:drug effects*; D012008:Recurrence; D012646:Self Administration
chemical_list: D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D018491:Dopamine Agonists; D010627:Phenethylamines; D011720:Pyrazoles; D011743:Pyrimidines; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D019257:Quinpirole; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; C416650:SCH 442416