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THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats.

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Psychology, Washington State University, Pullman, Washington 99164-4820, USA. awakley@wsu.edu

    Source

    Behavioural pharmacology 22:5-6 2011 Sep pg 489-97

    MeSH

    Analgesics, Non-Narcotic
    Analgesics, Opioid
    Animals
    Discrimination Learning
    Disease Models, Animal
    Dose-Response Relationship, Drug
    Dronabinol
    Drug Interactions
    Locomotion
    Male
    Methadone
    Naltrexone
    Narcotic Antagonists
    Pain
    Rats
    Rats, Sprague-Dawley
    Receptors, Opioid, mu

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    21716095

    Citation

    * When formatting your citation, note that all book, journal, and database titles should be italicized* 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/abstract/THC_methadone_and_THC_naltrexone_interactions_on_discrimination_antinociception_and_locomotion_in_rats_ L2 - http://Insights.ovid.com/pubmed?pmid=21716095 DB - PRIME DP - Unbound Medicine ER -