title: Role of adenosine receptor subtypes in methamphetamine reward and reinforcement.
abstract: The neurobiology of methamphetamine (MA) remains largely unknown despite its high abuse liability. The present series of studies explored the role of adenosine receptors on MA reward and reinforcement and identified alterations in the expression of adenosine receptors in dopamine terminal areas following MA administration in rats. We tested whether stimulating adenosine A1 or A2A receptor subtypes would influence MA-induced place preference or MA self-administration on fixed and progressive ratio schedules in male Sprague-Dawley rats. Stimulation of either adenosine A1 or A2A receptors significantly reduced the development of MA-induced place preference. Stimulating adenosine A1, but not A2A, receptors reduced MA self-administration responding. We next tested whether repeated experimenter-delivered MA administration would alter the expression of adenosine receptors in the striatal areas using immunoblotting. We observed no change in the expression of adenosine receptors. Lastly, rats were trained to self-administer MA or saline for 14 days and we detected changes in adenosine A1 and A2A receptor expression using immunoblotting. MA self-administration significantly increased adenosine A1 in the nucleus accumbens shell, caudate-putamen and prefrontal cortex. MA self-administration significantly decreased adenosine A2A receptor expression in the nucleus accumbens shell, but increased A2A receptor expression in the amygdala. These findings demonstrate that MA self-administration produces selective alterations in adenosine receptor expression in the nucleus accumbens shell and that stimulation of adenosine receptors reduces several behavioral indices of MA addiction. Together, these studies shed light onto the neurobiological alterations incurred through chronic MA use that may aid in the development of treatments for MA addiction.
authors.affiliation: Department of Psychology and Neuroscience and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Kavanagh
authors.affiliation: Department of Psychology and Neuroscience and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Drew C
authors.initials: DC
authors.lastname: Schreiner
authors.affiliation: Department of Psychology and Neuroscience and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Sophia C
authors.initials: SC
authors.lastname: Levis
authors.affiliation: Department of Psychology and Neuroscience and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
authors.forename: Casey E
authors.initials: CE
authors.lastname: O'Neill
authors.affiliation: Department of Psychology and Neuroscience and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA; Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA. Electronic address: Ryan.Bachtell@Colorado.edu.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Bachtell
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000697:Central Nervous System Stimulants; D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C048599:N(6)-cyclopentyladenosine; D008694:Methamphetamine; D000241:Adenosine
keywords: Place conditioning; Psychostimulant; Purine; Self-administration