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Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice.

C R Kasten, Y Zhang, S L Boehm

Pharmacology, Biochemistry, and Behavior December 2017 DOI: 10.1016/j.pbb.2017.10.012 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Controlled experimental study in mice Peer reviewed
Population Male inbred C57Bl/6J and DBA/2J mice
Intervention Δ9-tetrahydrocannabinol (THC)
Dose 10 mg/kg
Duration Six injections; assessments at 4 weeks and 5 weeks after the last injection
Measures novel object recognition task, elevated plus maze, open field, CB1R protein expression
Topics Anxiety Cannabis
Keywords Adolescence Cb1r Cannabinoids Memory
Key findings Repeated THC disrupted later object recognition memory in both mouse strains when given during adolescence, while adult exposure in C57Bl/6J mice appeared to improve a deficit present in vehicle-treated adults. Adolescent-treated mice also maintained higher CB1 receptor protein expression than adult-treated mice five weeks after the last injection, suggesting adolescence is a period of particular susceptibility to lasting THC effects.

Abstract

Use of exogenous cannabinoids disrupts the fine-tuned endocannabinoid receptor system, possibly leading to alterations in cognition, memory, and emotional processes that endure long after cannabinoid use has stopped. Long-term adolescent use may uniquely disrupt these behaviors when compared to adult use. The current study explored the acute and long-term behavioral effects of six 10mg/kg Δ9-tetrahydrocannabinol (THC) injections across the adolescent or early adult period in male inbred C57Bl/6J and DBA/2J mice. The acute and prolonged effects of THC on object memory using the novel object recognition task, unconditioned anxiety in the elevated plus maze and open field, and sedative effects in the open field were examined. Acute THC treatment resulted in anxiogenic activity in both strains, but only caused sedation in B6 mice. Repeated THC treatment resulted in a protracted effect on object recognition, but not unconditioned anxiety, assessed 4weeks later. In both strains, an adolescent history of THC treatment disrupted later object recognition. Interestingly, in B6 mice an adult history of THC exposure appeared to rescue a deficit in object recognition observed in vehicle-treated adults. Repeated THC administration also produced a protracted effected on CB1R protein expression. Animals treated with THC in adolescence maintained increased levels of CB1R protein expression compared to their adult THC-treated counterparts at five weeks following the last injection. These results indicate that THC use may have long-lasting effects with adolescence being a unique period of susceptibility.

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