Assessment of Acute Motor Effects and Tolerance Following Self‐Administration of Alcohol and Edible ∆⁹‐Tetrahydrocannabinol in Adolescent Male Mice

Abstract

IIBackground: Cannabinoids and their principle psychoactive target, the cannabinoid type 1 receptor (CB1R), impact a number of alcohol-related properties, and although alcohol and cannabis are often co-used, particularly in adolescence, few animal models of this phenomenon exist. We modeled the couse of alcohol and Δ 9 -tetrahydrocannabinol (THC) in adolescent mice using ingestive methods popular during this developmental period in humans, namely binge-drinking and edible THC. With this model, we assessed levels of use, acute effects, and tolerance to each substance.Methods: Adolescent male C57BL/6J mice had daily, limited access to 1 of 2 edible doughs (THC or control), to 1 of 2 fluids (ethanol (EtOH) or water), and in 1 of 2 orders (dough-fluid or fluiddough). Home cage locomotor activity was recorded both during access and after access. On the day following the final access session, a subset of mice were assessed for functional and metabolic tolerance to alcohol using accelerating rotarod and blood EtOH concentrations, respectively. The remaining mice were assessed for tolerance to THC-induced hypothermia, and whole-brain CB1R expression was assessed in all mice.Results: EtOH intake was on par with levels previously reported in adolescent mice. Edible THC was well-consumed, but consumption decreased at the highest dose provided. Locomotor activity increased following EtOH intake and decreased following edible THC consumption, and edible THC increased fluid intake in general. The use of alcohol produced neither functional nor metabolic tolerance to an alcohol challenge. However, the use of edible THC impaired subsequent drug-free rotarod performance and was associated with a reduction in THC's hypothermic effect.Conclusions: Adolescent mice self-administered both alcohol and edible THC to a degree sufficient to acutely impact locomotor activity. However, only edible THC consumption had lasting effects during short-term abstinence. Thus, this adolescent co-use model could be used to explore sex differences in self-administration and the impact substance co-use might have on other domains such as mood and cognition.

Effects of ethanol on mechanical allodynia and dynamic weight bearing in male and female mice with spared nerve injury

“…However, this does not preclude the possibility that higher doses of EtOH produce motor impairment. Indeed, impaired performance in the rotarod test occurs after administration of the higher doses of EtOH used in this study (Pandey, 2012;Smoker et al, 2019;Tornberg et al, 2007), which may contribute to the increased paw withdraw thresholds observed in both SNI and sham control animals following administration of the higher doses of EtOH. One challenge in interpreting DWB data in nerve injury models is determining whether the changes in weight bearing are observed due to the pain and hypersensitivity caused by the injury or other aspects of the injury, such as motor deficits (Sik Naa et al, 1996).…”

Der Einfluss von (-)-Δ9-trans- Tetrahydrocannabinol und Cannabidiol auf die Alzheimer-Pathologie im 5XFAD-Mausmodell

“…Ebenfalls unbeeinträchtigt von einer Behandlung mit THC blieb auch die motorische Ausdauer, Koordination und das Lernverhalten der weiblichen 5XFAD-Mäuse im Rotarod-Test. Untersuchte man die motorische Aktivität von C57BL/6J-Mäusen im eigenen Käfig, zeigte sich nach direkter THC-Einnahme eine signifikante Abnahme der motorischen Aktivität(Smoker et al 2019). Da sich jedoch vor allem in Angsttests eine signifikant geringer zurückgelegte Distanz zeigte, sollte dies unbedingt im Zusammenhang mit einer gesteigerten Ängstlichkeit interpretiert werden(Ennaceur 2014;Lutz et al 2015).…”