High-THCCannabisSmoke Impairs Incidental Memory Capacity in Spontaneous Tests of Novelty Preference for Objects and Odors in Male Rats

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Abstract Working memory is an executive function that orchestrates the use of limited amounts of information, referred to as working memory capacity, in cognitive functions.Cannabisexposure impairs working memory in humans; however, it is unclear whetherCannabisfacilitates or impairs rodent working memory and working memory capacity. The conflicting literature in rodent models may be at least partly because of the use of drug exposure paradigms that do not closely mirror patterns of humanCannabisuse. Here, we used an incidental memory capacity paradigm where a novelty preference is assessed after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in test variations with sets of identical [identical stimuli test (IST)] and different [different stimuli test (DST)] stimuli (three or six) for low-memory and high-memory loads, respectively. Additionally, we developed a human-machine hybrid behavioral quantification approach which supplements stopwatch-based scoring with supervised machine learning-based classification. After validating the spontaneous IST and DST in male rats, 6-item test versions with the hybrid quantification method were used to evaluate the impact of acute exposure to high-Δ9-tetrahydrocannabinol (THC) or high-CBDCannabissmoke on novelty preference. Under control conditions, male rats showed novelty preference in all test variations. We found that high-THC, but not high-CBD,Cannabissmoke exposure impaired novelty preference for objects under a high-memory load. Odor-based recognition deficits were seen under both low-memory and high-memory loads only following high-THC smoke exposure. Ultimately, these data show thatCannabissmoke exposure impacts incidental memory capacity of male rats in a memory load-dependent, and stimuli-specific manner.

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