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Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats.
Psychopharmacology (Berl) 2004; 175(3):360-6P

Abstract

RATIONALE

Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component delta9-tetrahydrocannabinol (delta9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats.

METHODS

To determine the effects of pretreatment with delta9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of delta9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of delta9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of delta9-THC.or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with delta9-THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle.

RESULTS

delta9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own.

CONCLUSIONS

These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning.

Authors+Show Affiliations

Department of Psychology, Wilfrid Laurier University, Waterloo, ON, Canada. lparker@wlu.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15138755

Citation

Parker, Linda A., et al. "Effect of Low Doses of Delta9-tetrahydrocannabinol and Cannabidiol On the Extinction of Cocaine-induced and Amphetamine-induced Conditioned Place Preference Learning in Rats." Psychopharmacology, vol. 175, no. 3, 2004, pp. 360-6.
Parker LA, Burton P, Sorge RE, et al. Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmacology (Berl). 2004;175(3):360-6.
Parker, L. A., Burton, P., Sorge, R. E., Yakiwchuk, C., & Mechoulam, R. (2004). Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. Psychopharmacology, 175(3), pp. 360-6.
Parker LA, et al. Effect of Low Doses of Delta9-tetrahydrocannabinol and Cannabidiol On the Extinction of Cocaine-induced and Amphetamine-induced Conditioned Place Preference Learning in Rats. Psychopharmacology (Berl). 2004;175(3):360-6. PubMed PMID: 15138755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of low doses of delta9-tetrahydrocannabinol and cannabidiol on the extinction of cocaine-induced and amphetamine-induced conditioned place preference learning in rats. AU - Parker,Linda A, AU - Burton,Page, AU - Sorge,Robert E, AU - Yakiwchuk,Christine, AU - Mechoulam,Raphael, PY - 2004/5/13/pubmed PY - 2005/2/3/medline PY - 2004/5/13/entrez SP - 360 EP - 6 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 175 IS - 3 N2 - RATIONALE: Using the place-preference conditioning paradigm, we evaluated the potential of the two most prominent cannabinoids found in marijuana, the psychoactive component delta9-tetrahydrocannabinol (delta9-THC) and the nonpsychoactive component cannabidiol (CBD), to potentiate extinction of a cocaine-induced and an amphetamine-induced conditioned place preference in rats. METHODS: To determine the effects of pretreatment with delta9-THC or CBD on extinction, a cocaine-induced and amphetamine-induced place preference was first established. Rats were then given an extinction trial, during which they were confined to the treatment-paired floor for 15 min. Thirty minutes prior to the extinction trial, they were injected with a low dose of delta9-THC (0.5 mg/kg), CBD (5 mg/kg) or vehicle. The potential of the CB1 receptor antagonist, SR141716, to reverse the effects of delta9-THC or CBD was also evaluated. To determine the hedonic effects of CBD, one distinctive floor was paired with CBD (5 mg/kg) and another with saline. Finally, to determine the effect of delta9-THC.or CBD on the establishment and/or the expression of a place preference during four cycles of conditioning trials, rats were injected with delta9-THC (0.25-1 mg/kg), CBD (5 mg/kg) or vehicle 25 min prior to receiving an injection of amphetamine followed by placement on the treatment floor; on alternate days, they received injections of vehicle followed by saline and placement on the nontreatment floor. The rats then received two test trials; on one trial they were pretreated with the cannabinoid and on the other trial with vehicle. RESULTS: delta9-THC and CBD potentiated the extinction of both cocaine-induced and amphetamine-induced conditioned place preference learning, and this effect was not reversed by SR141716. The cannabinoids did not affect learning or retrieval, and CBD was not hedonic on its own. CONCLUSIONS: These results are the first to show that both delta9-THC, which acts on both CB 1 and CB2 receptors, and CBD, which does not bind to CB1 or CB2 receptors, potentiate the extinction of conditioned incentive learning. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/15138755/Effect_of_low_doses_of_delta9_tetrahydrocannabinol_and_cannabidiol_on_the_extinction_of_cocaine_induced_and_amphetamine_induced_conditioned_place_preference_learning_in_rats_ L2 - https://dx.doi.org/10.1007/s00213-004-1825-7 DB - PRIME DP - Unbound Medicine ER -