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CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action.
Psychopharmacology (Berl) 2011; 216(3):323-31P

Abstract

RATIONALE

Cannabinoids have recently been identified as potential neuronal modulators of pruritic response, representing a potential target in the treatment of itch associated with a variety of pathophysiologic conditions. While the selective CB(1) receptor antagonist rimonabant is an established pruritic agent in both animal and clinical testing, its receptor mechanism of action and anatomical loci remain unclear.

OBJECTIVE

The purpose of this study was to determine whether CB(1) receptor blockade is critical to rimonabant-induced scratching and to identify differences in scratching response based on different routes of administration. Furthermore, experiments were designed to elucidate any evidence as to whether rimonabant elicits scratching behavior through common immunologic hypersensitivity mechanisms.

RESULTS

Rimonabant was equally effective at producing scratching via intraperitoneal and local subcutaneous injection. This compound also produced an intense scratching response when administered intrathecally, but had no effects after intracerebroventricular administration. Repeated administration of rimonabant led to a decreased magnitude of scratching. While rimonabant-induced scratching was not attenuated either by pretreatment with the H(1) receptor antagonist loratadine or in mast cell-deficient mice, it lacked efficacy in CB(1) (-/-) mice.

CONCLUSIONS

Rimonabant is a potent and fully effective pruritogen when administered spinally or systemically and requires CB(1) receptors to induce scratching, suggesting an important spinal CB(1) receptor component of action. The lack of responsiveness to H(1) antagonism or mast cell deficiency supports previous findings that cannabinoids modulate itch through neuronal mechanisms, and not by traditional hypersensitivity activation.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21340468

Citation

Schlosburg, Joel E., et al. "CB1 Receptors Mediate Rimonabant-induced Pruritic Responses in Mice: Investigation of Locus of Action." Psychopharmacology, vol. 216, no. 3, 2011, pp. 323-31.
Schlosburg JE, O'Neal ST, Conrad DH, et al. CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology (Berl). 2011;216(3):323-31.
Schlosburg, J. E., O'Neal, S. T., Conrad, D. H., & Lichtman, A. H. (2011). CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology, 216(3), pp. 323-31. doi:10.1007/s00213-011-2224-5.
Schlosburg JE, et al. CB1 Receptors Mediate Rimonabant-induced Pruritic Responses in Mice: Investigation of Locus of Action. Psychopharmacology (Berl). 2011;216(3):323-31. PubMed PMID: 21340468.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. AU - Schlosburg,Joel E, AU - O'Neal,Scott T, AU - Conrad,Daniel H, AU - Lichtman,Aron H, Y1 - 2011/02/22/ PY - 2010/11/08/received PY - 2011/02/04/accepted PY - 2011/2/23/entrez PY - 2011/2/23/pubmed PY - 2011/12/13/medline SP - 323 EP - 31 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 216 IS - 3 N2 - RATIONALE: Cannabinoids have recently been identified as potential neuronal modulators of pruritic response, representing a potential target in the treatment of itch associated with a variety of pathophysiologic conditions. While the selective CB(1) receptor antagonist rimonabant is an established pruritic agent in both animal and clinical testing, its receptor mechanism of action and anatomical loci remain unclear. OBJECTIVE: The purpose of this study was to determine whether CB(1) receptor blockade is critical to rimonabant-induced scratching and to identify differences in scratching response based on different routes of administration. Furthermore, experiments were designed to elucidate any evidence as to whether rimonabant elicits scratching behavior through common immunologic hypersensitivity mechanisms. RESULTS: Rimonabant was equally effective at producing scratching via intraperitoneal and local subcutaneous injection. This compound also produced an intense scratching response when administered intrathecally, but had no effects after intracerebroventricular administration. Repeated administration of rimonabant led to a decreased magnitude of scratching. While rimonabant-induced scratching was not attenuated either by pretreatment with the H(1) receptor antagonist loratadine or in mast cell-deficient mice, it lacked efficacy in CB(1) (-/-) mice. CONCLUSIONS: Rimonabant is a potent and fully effective pruritogen when administered spinally or systemically and requires CB(1) receptors to induce scratching, suggesting an important spinal CB(1) receptor component of action. The lack of responsiveness to H(1) antagonism or mast cell deficiency supports previous findings that cannabinoids modulate itch through neuronal mechanisms, and not by traditional hypersensitivity activation. SN - 1432-2072 UR - https://www.unboundmedicine.com/medline/citation/21340468/abstract/CB1_receptors_mediate_rimon L2 - https://dx.doi.org/10.1007/s00213-011-2224-5 DB - PRIME DP - Unbound Medicine ER -