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Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew.

Abstract

We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1) receptors in distinct loci.

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  • Publisher Full Text
  • Authors+Show Affiliations

    Department of Pharmacology, Kirksville College of Osteopathic Medicine, 800 West Jefferson Street, Kirksville, MO 63501, USA. ndarmani@kcom.edu

    Source

    MeSH

    Animals
    Antiemetics
    Antineoplastic Agents
    Bornanes
    Cisplatin
    Dronabinol
    Female
    Injections, Intraperitoneal
    Male
    Motor Activity
    Piperidines
    Pyrazoles
    Receptors, Cannabinoid
    Receptors, Drug
    Rimonabant
    Shrews
    Vomiting

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    11420092

    Citation

    Darmani, N A.. "Delta-9-tetrahydrocannabinol Differentially Suppresses Cisplatin-induced Emesis and Indices of Motor Function Via Cannabinoid CB(1) Receptors in the Least Shrew." Pharmacology, Biochemistry, and Behavior, vol. 69, no. 1-2, 2001, pp. 239-49.
    Darmani NA. Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew. Pharmacol Biochem Behav. 2001;69(1-2):239-49.
    Darmani, N. A. (2001). Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew. Pharmacology, Biochemistry, and Behavior, 69(1-2), pp. 239-49.
    Darmani NA. Delta-9-tetrahydrocannabinol Differentially Suppresses Cisplatin-induced Emesis and Indices of Motor Function Via Cannabinoid CB(1) Receptors in the Least Shrew. Pharmacol Biochem Behav. 2001;69(1-2):239-49. PubMed PMID: 11420092.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB(1) receptors in the least shrew. A1 - Darmani,N A, PY - 2001/6/23/pubmed PY - 2001/9/8/medline PY - 2001/6/23/entrez SP - 239 EP - 49 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 69 IS - 1-2 N2 - We have recently shown that the cannabinoid CB(1) receptor antagonist, SR 141716A, produces emesis in the least shrew (Cryptotis parva) in a dose- and route-dependent manner. This effect was blocked by delta-9-tetrahydrocannabinol (Delta(9)-THC). The present study investigates the cannabinoid receptor mechanisms by which Delta(9)-THC produces its antiemetic effects against cisplatin (20 mg/kg, i.p.)-induced emesis as well as its cannabimimetic activity profile (motor reduction) in the least shrew. Intraperitoneal administration of Delta(9)-THC (1, 2.5, 5 and 10 mg/kg) dose-dependently reduced both the percentage of animals vomiting (ID(50)=1.8+/-1.6 mg/kg) and the frequency of vomits (ID(50)=0.36+/-1.18 mg/kg) in a potent manner. The lowest significantly effective antiemetic dose of Delta(9)-THC for the latter emesis parameters was 2.5 mg/kg. Although Delta(9)-THC reduced the frequency of vomits up to 98%, it failed to completely protect all tested shrews from vomiting (80% protection). The cannabinoid CB(1) antagonist (SR 141716A) and not the CB(2) antagonist (SR 144528), reversed the antiemetic effects of Delta(9)-THC in a dose-dependent fashion. Delta(9)-THC (1, 5, 10 and 20 mg/kg, ip) suppressed locomotor parameters (spontaneous locomotor activity, duration of movement and rearing frequency) in a biphasic manner and only the 20-mg/kg dose simultaneously suppressed the triad of locomotor parameters to a significant degree. Subcutaneous (1-10 mg/kg) and intraperitoneal (0.05-40 mg/kg) injection of some doses of SR 141716A caused significant reductions in one or more components of the triad of locomotor parameters but these reductions were not dose dependent. Subcutaneous injection of SR 141716A (0.2, 1, 5 and 10 mg/kg) reversed the motor suppressant effects of a 20-mg/kg dose of Delta(9)-THC (ip) in a dose-dependent manner. Relative to its motor suppressant effects, Delta(9)-THC is a more potent antiemetic agent. Both effects are probably mediated via CB(1) receptors in distinct loci. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/11420092/Delta_9_tetrahydrocannabinol_differentially_suppresses_cisplatin_induced_emesis_and_indices_of_motor_function_via_cannabinoid_CB_1__receptors_in_the_least_shrew_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(01)00531-7 DB - PRIME DP - Unbound Medicine ER -