RT Journal Article
SR Electronic
T1 Sex-differences in acute Δ9-THC-induced antinociception are strain-specific
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 474
DO 10.1124/jpet.122.555730
VO 385
IS S3
A1 Lulek, Courtney
A1 Maulik, Malabika
A1 Mitra, Swarup
A1 Morgan, Daniel
A1 Henderson-Redmond, Angela N.
YR 2023
UL http://jpet.aspetjournals.org/content/385/S3/474.abstract
AB Abstract ID 55573Poster Board 474Though cannabinoids are being increasingly used for their pain-relieving effects, tolerance to these effects, including those of delta-9-tetrahydrocannabinol (?9-THC), may limit their clinical efficacy. With more women than men now using medical cannabis for pain relief, it is crucial we understand how biological sex may influence cannabinoid-mediated antinociception and subsequent tolerance. Likewise, few studies have considered whether the efficacy of cannabinoids may vary as a function of genetics. Though studies in rats consistently find female rats to be more sensitive to the acute antinociceptive effects of cannabinoids than males, work in our lab consistently finds the converse. Studies in our lab primarily utilize mice on a C57BL6/J (B6) background. Consequently, not only is there is little genetic variation among our B6 mice, but it remains unknown whether the sex-specific effects we observe in B6 mice extend to other mouse strains. Therefore, the purpose of the present study is to examine whether our observed sex differences in Δ9-THC-induced antinociception and tolerance are strain-dependent. Male and female B6, DBA, AKR, and CBA mice were assessed for differences in acute Δ9-THC-induced antinociception and hypothermia prior to and following seven days of once-daily Δ9-THC administration. Consistent with our previous studies, male B6 mice were more sensitive to the acute antinociceptive effects of Δ9-THC than female B6 mice, an effect which correlated with differences in B6 CB1 mRNA expression in the PAG and dissipated with age. While DBA and CBA female mice showed increased Δ9-THC-antinociception compared to male littermates at 30 and 10 mg/kg Δ9-THC, respectively, these effects dissipated at higher doses, revealing that dose of Δ9-THC may also be important. Overall, CBA mice were much more sensitive to Δ9-THC-induced antinociception while AKR mice were much less responsive. Despite the heterogeneity in Δ9-THC-induced antinociception, there was little variability in Δ9-THC-induced hypothermia as a function of either sex or mouse strain. Likewise, across all strains, female mice were faster to develop tolerance or developed tolerance at the same rate as male littermates. Taken together, these studies highlight the therapeutic potential of Δ9-THC in pain management and underscore the importance of considering not only Δ9-THC dose as a function of sex, but potentially genetic differences among various populations when evaluating their clinical utility.Support/Funding Information: DA044999