Role of dopamine D-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 D-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 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.

CONCLUSIONS

These results demonstrate the sufficiency of dopamine D receptors to reinstate MA seeking that is inhibited when combined with adenosine A receptor stimulation.