High-THC Cannabis smoke impairs incidental memory capacity in spontaneous tests of novelty preference for objects and odors in male rats

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. Cannabis exposure impairs working memory in humans; however, it is unclear if Cannabis facilitates or impairs rodent working memory and working memory capacity. The conflicting literature in rodent models may be at least partly due to the use of drug exposure paradigms that do not closely mirror patterns of human Cannabis use. 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 (IST) and different (DST) stimuli (3 or 6) for low- 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-THC or high-CBD Cannabis smoke on novelty preference. Under control conditions, male rats showed novelty preference in all test variations. We found that high-THC, but not high-CBD, Cannabis smoke exposure impaired novelty preference for objects under a high-memory load. Odor-based recognition deficits were seen under both low-, and high-memory loads only following high-THC smoke exposure. Ultimately, these data show that Cannabis smoke exposure impacts incidental memory capacity of male rats in a memory load-dependent, and stimuli-specific manner.

Significance Statement

Incidental memory refers to the limited amount of information encoded by chance during behavior. How psychoactive drug exposure affects incidental memory is poorly understood, particularly for Cannabis exposure. To address this question, we validated object- and odor-based spontaneous incidental memory tests in male rats using a novel human-machine hybrid scoring method. Using these tests, we show exposure to high-THC, but not high-CBD, Cannabis smoke impairs incidental memory under high-memory loads in object-based tests and both high- and low-memory loads in the odor-based tests. Our results highlight cannabinoid-specific effects on incidental memory in male rats using a validated Cannabis smoke exposure method, which have broad implications for the impacts of human use of Cannabis on cognition.