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Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine.
Pharmacol Biochem Behav 2001 May-Jun; 69(1-2):181-8PB

Abstract

The availability of the cannabinoid antagonist, SR 141716A, to precipitate withdrawal following repeated cannabinoid administration provides a model to investigate the mechanisms underlying cannabinoid dependence as well as potential treatments to alleviate withdrawal symptoms. The goal of the present study was to determine whether SR 141716A-precipitated withdrawal symptoms in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant mice could be alleviated by either readministration of Delta(9)-THC or clonidine, an alpha(2)-receptor agonist. SR 141716A elicited paw tremors in Delta(9)-THC-tolerant mice, but produced a significant increase in head shakes independently of repeated Delta(9)-THC treatment. Readministration of Delta(9)-THC, following SR 141716A-precipitated withdrawal, reversed paw tremors (ED(50)=9.9 mg/kg), but failed to reduce head shaking behavior. Clonidine reversed SR 141716A-precipitated paw tremors (ED(50)=0.18 mg/kg) and blocked head shakes at all doses tested. The reversal effects did not appear to be the result of motor impairment because neither decreases in spontaneous locomotor activity nor motor incoordination, as assessed in the inverted screen test, could account for the effects. These findings suggest that SR 141716A precipitates paw tremors in mice by competing with Delta(9)-THC at the CB(1) receptor, though it also produced head shaking in nondependent animals. Finally, the observation that clonidine alleviated SR 141716A-precipitated paw tremors suggests its potential as a treatment for cannabinoid dependence.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, P.O. Box 980613, 245 North 15th Street, Richmond, VA 23298-0613, USA. alichtma@hsc.vcu.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11420084

Citation

Lichtman, A H., et al. "Precipitated Cannabinoid Withdrawal Is Reversed By Delta(9)-tetrahydrocannabinol or Clonidine." Pharmacology, Biochemistry, and Behavior, vol. 69, no. 1-2, 2001, pp. 181-8.
Lichtman AH, Fisher J, Martin BR. Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. Pharmacol Biochem Behav. 2001;69(1-2):181-8.
Lichtman, A. H., Fisher, J., & Martin, B. R. (2001). Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. Pharmacology, Biochemistry, and Behavior, 69(1-2), pp. 181-8.
Lichtman AH, Fisher J, Martin BR. Precipitated Cannabinoid Withdrawal Is Reversed By Delta(9)-tetrahydrocannabinol or Clonidine. Pharmacol Biochem Behav. 2001;69(1-2):181-8. PubMed PMID: 11420084.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Precipitated cannabinoid withdrawal is reversed by Delta(9)-tetrahydrocannabinol or clonidine. AU - Lichtman,A H, AU - Fisher,J, AU - Martin,B R, PY - 2001/6/23/pubmed PY - 2001/9/8/medline PY - 2001/6/23/entrez SP - 181 EP - 8 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 69 IS - 1-2 N2 - The availability of the cannabinoid antagonist, SR 141716A, to precipitate withdrawal following repeated cannabinoid administration provides a model to investigate the mechanisms underlying cannabinoid dependence as well as potential treatments to alleviate withdrawal symptoms. The goal of the present study was to determine whether SR 141716A-precipitated withdrawal symptoms in Delta(9)-tetrahydrocannabinol (Delta(9)-THC)-tolerant mice could be alleviated by either readministration of Delta(9)-THC or clonidine, an alpha(2)-receptor agonist. SR 141716A elicited paw tremors in Delta(9)-THC-tolerant mice, but produced a significant increase in head shakes independently of repeated Delta(9)-THC treatment. Readministration of Delta(9)-THC, following SR 141716A-precipitated withdrawal, reversed paw tremors (ED(50)=9.9 mg/kg), but failed to reduce head shaking behavior. Clonidine reversed SR 141716A-precipitated paw tremors (ED(50)=0.18 mg/kg) and blocked head shakes at all doses tested. The reversal effects did not appear to be the result of motor impairment because neither decreases in spontaneous locomotor activity nor motor incoordination, as assessed in the inverted screen test, could account for the effects. These findings suggest that SR 141716A precipitates paw tremors in mice by competing with Delta(9)-THC at the CB(1) receptor, though it also produced head shaking in nondependent animals. Finally, the observation that clonidine alleviated SR 141716A-precipitated paw tremors suggests its potential as a treatment for cannabinoid dependence. SN - 0091-3057 UR - https://www.unboundmedicine.com/medline/citation/11420084/Precipitated_cannabinoid_withdrawal_is_reversed_by_Delta_9__tetrahydrocannabinol_or_clonidine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(01)00514-7 DB - PRIME DP - Unbound Medicine ER -