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THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.
Behav Pharmacol. 2011 Sep; 22(5-6):489-97.BP

Abstract

This study examined cannabinoid-opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose-dependently increased THC-appropriate lever responding and decreased response rate. THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding up to doses that decreased response rate. When combined with THC, methadone (1.0 mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did enhance THC antinociception. These results suggest that μ-opioid receptor agonists can disrupt the discriminative stimulus effects of cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically drug-exposed subjects. Further research is required to determine whether opioid enhancement of cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically drug-exposed subjects.

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Authors+Show Affiliations

Wakley AA
Department of Psychology, Washington State University, Pullman, Washington 99164-4820, USA. awakley@wsu.edu
Craft RM
No affiliation info available

MeSH

Analgesics, Non-NarcoticAnalgesics, OpioidAnimalsDiscrimination LearningDisease Models, AnimalDose-Response Relationship, DrugDronabinolDrug InteractionsLocomotionMaleMethadoneNaltrexoneNarcotic AntagonistsPainRatsRats, Sprague-DawleyReceptors, Opioid, mu

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21716095

Citation

Wakley, Alexa A., and Rebecca M. Craft. "THC-methadone and THC-naltrexone Interactions On Discrimination, Antinociception, and Locomotion in Rats." Behavioural Pharmacology, vol. 22, no. 5-6, 2011, pp. 489-97.
Wakley AA, Craft RM. THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats. Behav Pharmacol. 2011;22(5-6):489-97.
Wakley, A. A., & Craft, R. M. (2011). THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats. Behavioural Pharmacology, 22(5-6), 489-97. https://doi.org/10.1097/FBP.0b013e328348ed22
Wakley AA, Craft RM. THC-methadone and THC-naltrexone Interactions On Discrimination, Antinociception, and Locomotion in Rats. Behav Pharmacol. 2011;22(5-6):489-97. PubMed PMID: 21716095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats. AU - Wakley,Alexa A, AU - Craft,Rebecca M, PY - 2011/7/1/entrez PY - 2011/7/1/pubmed PY - 2011/12/14/medline SP - 489 EP - 97 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 22 IS - 5-6 N2 - This study examined cannabinoid-opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose-dependently increased THC-appropriate lever responding and decreased response rate. THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding up to doses that decreased response rate. When combined with THC, methadone (1.0 mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did enhance THC antinociception. These results suggest that μ-opioid receptor agonists can disrupt the discriminative stimulus effects of cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically drug-exposed subjects. Further research is required to determine whether opioid enhancement of cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically drug-exposed subjects. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/21716095/THC_methadone_and_THC_naltrexone_interactions_on_discrimination_antinociception_and_locomotion_in_rats_ L2 - https://doi.org/10.1097/FBP.0b013e328348ed22 DB - PRIME DP - Unbound Medicine ER -