title: Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys.
abstract: BACKGROUND
  Δ(9)-tetrahydrocannabinol (Δ(9)-THC) modifies dopamine efflux. However, the extent to which cannabinoid and dopamine drugs modify each other's behavioral effects has not been fully established.
  
  
  OBJECTIVE
  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 (n = 5) discriminated Δ(9)-THC (0.1 mg/kg i.v.) from vehicle while responding under a fixed ratio 5 schedule of stimulus-shock termination. A separate group (n = 6) of monkeys responded under the same schedule, received daily Δ(9)-THC (1 mg/kg/12 h s.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 Δ(9)-THC daily.
  
  
  RESULTS
  Rimonabant antagonized the Δ(9)-THC discriminative stimulus and a dose of Δ(9)-THC greater than the daily treatment attenuated the rimonabant discriminative stimulus. In monkeys discriminating Δ(9)-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 Δ(9)-THC. In Δ(9)-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 Δ(9)-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 Δ(9)-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 Δ(9)-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.
authors.affiliation: Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Schulze
authors.forename: F Ivy
authors.initials: FI
authors.lastname: Carroll
authors.forename: Lance R
authors.initials: LR
authors.lastname: McMahon
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043882:Receptors, Cannabinoid / Q000502:physiology*; D000077285:Rimonabant; D014326:Tropanes / Q000494:pharmacology
chemical_list: C095429:3-(4'-chlorophenyl)-2-(3'-phenylisoxazol-5'-yl)tropane; D050483:Dopamine Plasma Membrane Transport Proteins; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D014326:Tropanes; D013759:Dronabinol; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol; D007099:Imipramine; D000077285:Rimonabant