Role of dopamine D2-like receptors and their modulation by adenosine receptor stimulation in the reinstatement of methamphetamine seeking.
RATIONALE AND OBJECTIVE: 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 D2-like receptors in MA seeking and identified the interactive effects of adenosine receptor stimulation. METHODS: 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. RESULTS: An increase in MA seeking was observed following the administration of the dopamine D2-like agonist, quinpirole, or the D3 receptor agonist, 7-OH-DPAT. Stimulation of D2 or D4 receptors was ineffective at inducing MA seeking. Quinpirole-induced MA seeking was inhibited by D3 receptor antagonism (SB-77011A or PG01037), an adenosine A1 agonist, CPA, and an adenosine A2A agonist, CGS 21680. MA seeking induced by a MA priming injection or D3 receptor stimulation was inhibited by a pretreatment with the adenosine A1 agonist, CPA, but not the adenosine A2A agonist, CGS 21680. CONCLUSIONS: These results demonstrate the sufficiency of dopamine D3 receptors to reinstate MA seeking that is inhibited when combined with adenosine A1 receptor stimulation.