Lasting effects of repeated ∆9‐tetrahydrocannabinol vapour inhalation during adolescence in male and female rats

Author(s): Nguyen, Jacques D; Creehan, Kevin M; Kerr, Tony M; Taffe, Michael A | Abstract: Background and purposeAdolescents are regularly exposed to ∆9 -tetrahydrocannabinol (THC) via smoking and, more recently, vaping cannabis extracts. Growing legalization of cannabis for medical and recreational purposes, combined with decreasing perceptions of harm, makes it increasingly important to determine the consequences of frequent adolescent exposure for motivated behaviour and lasting tolerance in response to THC.Experimental approachesMale and female rats inhaled THC vapour, or that from the propylene glycol (PG) vehicle, twice daily for 30nmin from postnatal day (PND) 35-39 and PND 42-46 using an e-cigarette system. Thermoregulatory responses to vapour inhalation were assessed by radio-telemetry during adolescence and from PND 86-94. Chow intake was assessed in adulthood. Blood samples were obtained from additional adolescent groups following initial THC inhalation and after 4ndays of twice daily exposure. Additional groups exposed repeatedly to THC or PG during adolescence were evaluated for intravenous self-administration of oxycodone as adults.Key resultsFemale, not male, adolescents developed tolerance to the hypothermic effects of THC inhalation in the first week of repeated exposure despite similar plasma THC levels. Each sex exhibited tolerance to THC hypothermia in adulthood after repeated adolescent THC. However, enhanced potency was found in females. Repeated THC male rats consumed more food than their PG-treated control group, without significant bodyweight differences. Adolescent THC did not alter oxycodone self-administration in either sex but increased fentanyl self-administration in females.Conclusions and implicationsRepeated THC vapour inhalation in adolescent rats has lasting consequences observable in adulthood.