Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys

David R. Schulze, F. Ivy Carroll, Lance R. McMahon

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Rationale δ9-tetrahydrocannabinol (δ9- THC) modifies dopamine efflux. However, the extent to which cannabinoid and dopamine drugs modify each other's behavioral effects has not been fully established. Objectives This study examined dopamine releasers and/or transport inhibitors alone and in combination with cannabinoids in two drug discrimination assays. Methods Experimentally and pharmacologically experienced rhesus monkeys (n05) discriminated δ9-THC (0.1 mg/kg i.v.) from vehicle while responding under a fixed ratio 5 schedule of stimulus-shock termination. A separate group (n06) of monkeys responded under the same schedule, received daily δ9-THC (1 mg/kg/12 hs.c.), and discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.), i.e., cannabinoid withdrawal, from vehicle. A sign of withdrawal sign (head shaking) was examined in monkeys receiving δ9-THC daily. Results Rimonabant antagonized the δ9-THC discriminative stimulus and a dose of δ9-THC greater than the daily treatment attenuated the rimonabant discriminative stimulus. In monkeys discriminating δ9-THC, the dopamine transporter ligands cocaine, amphetamine, bupropion, RTI 113, and RTI 177 produced a maximum of 2% responding on the drug lever and blocked the discriminative stimulus effects of δ9- THC. In δ9-THC treated monkeys discriminating rimonabant, the dopamine transporter ligands partially substituted for and increased the potency of rimonabant to produce discriminative stimulus effects. The dopamine antagonist haloperidol enhanced the δ9-THC discriminative stimulus without significantly modifying the rimonabant discriminative stimulus. Imipramine and desipramine, which have low affinity for dopamine transporters, were less effective in modifying either the δ9-THC or rimonabant discriminations. The dopamine transporter ligands and haloperidol attenuated head shaking, whereas imipramine and desipramine did not. Conclusions Dopamine release and/or inhibition of dopamine transport blocks detection of δ9-THC and is potentially the mechanism by which some therapeutics (e.g., bupropion) reduce the subjective effects of marijuana and enhance the subjective effects of marijuana withdrawal.

Original languageEnglish (US)
Pages (from-to)425-438
Number of pages14
Issue number3
StatePublished - Aug 2012


  • Cannabis
  • Delta-9-tetrahydrocannabinol
  • Dependence
  • Dopamine
  • Drug discrimination
  • Marijuana
  • Monkey
  • Rimonabant
  • Withdrawal

ASJC Scopus subject areas

  • Pharmacology


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