Sex-specific mechanisms of tolerance for the cannabinoid agonists CP55,940 and delta-9-tetrahydrocannabinol (Δ
Tolerance to cannabinoids could limit their therapeutic potential. Male mice expressing a desensitization-resistant form (S426AS430A) of the type-1 cannabinoid receptor (CB Our objective was to determine whether female mice rely on the same molecular mechanisms for tolerance to the antinociceptive andor hypothermic effects of cannabinoids that we have previously reported in males. We determined whether the S426AS430A mutation differentially disrupts antinociceptive andor hypothermic tolerance to CP55,940 andor Δ The S426AS430A mutation conferred an enhanced antinociceptive response for ∆ Our results suggest that disruption of the GRKβarrestin2 pathway of desensitization alters tolerance to Δ