Role of dopamine D 2 -like receptors and their modulation by adenosine receptor stimulation in the reinstatement of methamphetamine seeking

• Published in: Psychopharmacology (Berlin, Germany) Germany), 2019-04, Vol.236 (4), p.1207
• Main Authors: Larson, Tracey A, Winkler, Madeline C, Stafford, Jacob, Levis, Sophia C, O'Neill, Casey E, Bachtell, Ryan K
• Format: Article
• Language: English
• Subjects: Adenosine A2 Receptor Agonists - pharmacology; Animals; Central Nervous System Stimulants - administration & dosage; Dopamine Agonists - pharmacology; Dose-Response Relationship, Drug; Drug-Seeking Behavior - drug effects; Drug-Seeking Behavior - physiology; Male; Methamphetamine - administration & dosage; Rats; Rats, Sprague-Dawley; Receptor, Adenosine A2A - metabolism; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - physiology; Self Administration
• ISSN: 1432-2072
• DOI: 10.1007/s00213-018-5126-y

Previous work has demonstrated that dopamine and adenosine receptors are involved in drug-seeking behaviors, yet the pharmacological interactions between these receptors in methamphetamine (MA) seeking are not well characterized. The present studies examined the role of the dopamine D -like receptors in MA seeking and identified the interactive effects of adenosine receptor stimulation. Adult male Sprague-Dawley rats were trained to lever press for MA in daily 2-h self-administration sessions on a fixed-ratio 1 schedule for 10 consecutive days. After 1 day of abstinence, lever pressing was extinguished in six daily extinction sessions. Treatments were administered systemically prior to a 2-h reinstatement test session. An increase in MA seeking was observed following the administration of the dopamine D -like agonist, quinpirole, or the D receptor agonist, 7-OH-DPAT. Stimulation of D or D receptors was ineffective at inducing MA seeking. Quinpirole-induced MA seeking was inhibited by D receptor antagonism (SB-77011A or PG01037), an adenosine A agonist, CPA, and an adenosine A agonist, CGS 21680. MA seeking induced by a MA priming injection or D receptor stimulation was inhibited by a pretreatment with the adenosine A agonist, CPA, but not the adenosine A agonist, CGS 21680. These results demonstrate the sufficiency of dopamine D receptors to reinstate MA seeking that is inhibited when combined with adenosine A receptor stimulation.