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Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys.
Psychopharmacology (Berl). 2012 Aug; 222(3):425-38.P

Abstract

RATIONALE

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.

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 (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+Show Affiliations

Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22374253

Citation

Schulze, David R., et al. "Interactions Between Dopamine Transporter and Cannabinoid Receptor Ligands in Rhesus Monkeys." Psychopharmacology, vol. 222, no. 3, 2012, pp. 425-38.
Schulze DR, Carroll FI, McMahon LR. Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys. Psychopharmacology (Berl). 2012;222(3):425-38.
Schulze, D. R., Carroll, F. I., & McMahon, L. R. (2012). Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys. Psychopharmacology, 222(3), 425-38. https://doi.org/10.1007/s00213-012-2661-9
Schulze DR, Carroll FI, McMahon LR. Interactions Between Dopamine Transporter and Cannabinoid Receptor Ligands in Rhesus Monkeys. Psychopharmacology (Berl). 2012;222(3):425-38. PubMed PMID: 22374253.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between dopamine transporter and cannabinoid receptor ligands in rhesus monkeys. AU - Schulze,David R, AU - Carroll,F Ivy, AU - McMahon,Lance R, Y1 - 2012/02/29/ PY - 2011/11/04/received PY - 2012/02/02/accepted PY - 2012/3/1/entrez PY - 2012/3/1/pubmed PY - 2012/12/10/medline SP - 425 EP - 38 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 222 IS - 3 N2 - RATIONALE: 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. 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 (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. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/22374253/Interactions_between_dopamine_transporter_and_cannabinoid_receptor_ligands_in_rhesus_monkeys_ L2 - https://dx.doi.org/10.1007/s00213-012-2661-9 DB - PRIME DP - Unbound Medicine ER -