Do you feel it now? Route of administration and Δ9-tetrahydrocannabinol-like discriminative stimulus effects of synthetic cannabinoids in mice

Abstract A recent push to provide more translationally relevant preclinical models for examination of pharmacological mechanisms underlying inhaled substances of abuse has resulted in the development of equipment and methods that allows exposure of freely moving rodents to aerosolized psychoactive drugs. In the present study, synthetic cannabinoids(CP55,940, AB-CHMINACA, and AMB-FUBINACA) were administered intraperitoneally (i.p.) or aerosolizedvia a modified electronic cigarettedevice. Subsequently, the compounds were evaluated in adult male and female C57/Bl6 mice trained to discriminate i.p. 5.6 mg/kg Δ 9 - tetrahydrocannabinol(THC) for food reinforcement. When administered i.p., THC and AB-CHMINACAwere equally potent at producing THC-like effects in both sexes, but CP55,940 and AMB-FUBINACAwere more potent in males. Upon aerosolexposure, all compounds continued to produce THC-like effects in both sexes, with AMB-FUBINACAremaining the most potent. In contrast, aerosolizedCP55,940 showed substantial decreases in potency in both sexes. Aerosolizednicotine did not substitute for THC in either sex. In females, aerosolizedcumyl-4CN-BINACA produced concentration-dependent increases in responding on the THC-associated nosepoke. In addition, the effects of an active concentration of AMB-FUBINACAwere reversed by rimonabant, suggesting CB 1 receptor mediation. These results show that synthetic cannabinoidsproduce THC-like effects when injected i.p. or after aerosolization. This study adds to a growing literature suggesting that evaluation of abuse liability of substances via aerosolexposure is feasible and may provide a translationally relevant method that allows for investigation of factors important to the abuse of drugs which humans typically smoke or vape.