Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chronic Use of the Synthetic Cannabinoid WIN 55,212-2 55 Modifies the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine

Version 1 : Received: 23 January 2023 / Approved: 27 January 2023 / Online: 27 January 2023 (06:16:10 CET)

A peer-reviewed article of this Preprint also exists.

Ibancovichi, J.A.; Chávez-Monteagudo, J.R.; Sánchez-Aparicio, P.; De Paz-Campos, M.A. Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine. Vet. Sci. 2023, 10, 310. Ibancovichi, J.A.; Chávez-Monteagudo, J.R.; Sánchez-Aparicio, P.; De Paz-Campos, M.A. Repeated Administration of the Cannabinoid WIN Alters the Isoflurane-Sparing Effect of Morphine and Dexmedetomidine. Vet. Sci. 2023, 10, 310.

Abstract

The effects of morphine (MOR) and dexmedetomidine (DEX) on the MAC of isoflurane were measured in rats chronically treated with the synthetic cannabinoid WIN 55,212-2 (WIN55). Methods: The MAC of isoflurane was determined in 32 male rats from expiratory samples at the time of tail clamping. The effects of morphine (MAC(ISO+MOR)) and dexmedetomidine (MAC(ISO+DEX)) on the MAC of isoflurane in untreated rats and rats treated for 21 days with WIN 55,212-2 (MAC(ISO+WIN55+MOR)) and (MAC(ISO+WIN55+DEX)) were measured. Prior to the administration of morphine and dexmedetomidine, the MAC of the isoflurane was measured in both untreated rats (MAC(ISO)) and those treated with WIN 55,212-2 (MAC(ISO+WIN55)). Results: The minimum alveolar concentration was measured as 1.32 ± 0.06 in the MAC(ISO) group and 1.69 ± 0.09 in the MAC(ISO+WIN55) group. The MAC of the MAC(ISO+MOR) group was 0.97 ± 0.02 (26% less than the control group, MAC(ISO)). MAC was measured as 1.55 ± 0.08 in the MAC(ISO+WIN55+MOR) group (8% less than the MAC(ISO+WIN55) group), 0.68 ± 0.10 in the MAC(ISO+DEX) group (48% less than the control group, MAC(ISO)), and 0.67 ± 0.08 in the MAC(ISO+WIN55+DEX) group (60% less than the MAC(ISO+WIN55) group). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. The sparing effect on isoflurane of morphine decreases in rats chronically treated with the synthetic cannabinoid, WIN 55,212-2. Dexmedetomidine increases its sparing effect on the minimum alveolar concentration of isoflurane in rats chronically treated with WIN 55,212-2.

Keywords

minimum alveolar concentration MAC; isoflurane; dexmedetomidine; morphine; synthetic cannabinoid WIN 55,212-2; rats

Subject

Medicine and Pharmacology, Anesthesiology and Pain Medicine

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