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Zyklophin, a short-acting kappa opioid antagonist, induces scratching in mice
DiMattio, K. M. Yakovleva, Tatyana Aldrich, Jane V. Cowan, A. Liu-Chen, Lee-Yuan
DiMattio, K. M.
Yakovleva, Tatyana
Aldrich, Jane V.
Cowan, A.
Liu-Chen, Lee-Yuan
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Abstract
It has been shown previously that norbinaltorphimine (norBNI) and 5΄-guanidinonaltrindole (5΄-GNTI), long-acting kappa opioid receptor (KOPR) antagonists, cause frenzied scratching in mice [1;2]. In the current study, we examined if zyklophin, a short-acting cyclic peptide KOPR antagonist, also elicited scratching behavior. When injected s.c. in the nape of the neck of male Swiss-Webster mice, zyklophin at doses of 0.1, 0.3 and 1 mg/kg induced dose-related hindleg scratching of the neck between 3 and 15 min after injection. Pretreating mice with norBNI (20 mg/kg, i.p.) at 18–20 hr before challenge with zyklophin (0.3 mg/kg) did not markedly affect scratching. Additionally, KOPR −/− mice given 0.3 mg/kg of zyklophin displayed similar levels of scratching as wild-type animals. The absence of KOPR in KOPR −/− mice was confirmed with ex vivo radioligand binding using [3H]U69,593. Taken together, our data suggest that the presence of kappa receptors is not required for the excessive scratching caused by zyklophin. Thus, zyklophin, similar to the structurally different KOPR antagonist 5΄-GNTI, appears to act at other targets to elicit scratching and potentially the sensation of itch.
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2014-03-20
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Elsevier
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Yakovleva_2015.pdf
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Itch, Scratching, Kappa opioid receptor, Kappa opioid receptor antagonist, Zyklophin
Citation
DiMattio, K. M., Yakovleva, T. V., Aldrich, J. V., Cowan, A., & Liu-Chen, L. Y. (2014). Zyklophin, a short-acting kappa opioid antagonist, induces scratching in mice. Neuroscience Letters, 563, 155–159. http://doi.org/10.1016/j.neulet.2014.01.022