Examining the impact of acute Cannabis exposure on short-term memory using novel and established rodent models
Date
2025-04-21
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0009-0000-5583-2750
Type
Thesis
Degree Level
Doctoral
Abstract
Short-term memory is defined as a limited amount of information temporarily held in conscious awareness. It is essential for daily functioning as its loss leads to complications observed in neurodegenerative and neuropsychiatric disorders. Short-term memory can be encoded either incidentally through spontaneous interactions or intentionally through manners that may require greater effort and engagement. How intoxicating drug exposure affects short-term memory is poorly understood, especially for drugs such as Cannabis. Most research on Cannabis focuses on its two main constituents: the intoxicating 9-tetrahydrocannabinol (THC) and the non-intoxicating cannabidiol (CBD). High demand exists for Cannabis research using translational methods of administration such as inhalation in preclinical models. This demand also exists for the development and use of appropriate tests to examine short-term memory in rodents. Short-term memory can be tested by investigating novelty recognition and working memory processes. We developed spontaneous incidental memory tests called the Identical Stimuli (IST) and the Different Stimuli (DST) Tests, with both object- and odor-based forms, which can be employed using varying memory loads. The IST has a low-memory load, and the DST has a comparatively higher-memory load. Rats I tested in these tests preferentially interacted with novel stimuli. We then used fiber photometry and chemogenetic techniques to highlight the role of the medial prefrontal cortex (mPFC) in enabling novelty detection under higher memory loads in odor-based tests. We observed an increase in calcium transients which was sustained throughout the interactions with novel stimuli in the odor-based DST but not in the odor-based IST. We also observed a decrease in novelty preference in the odor-based DST but not in the odor-based IST when modulating the activity of CaMKII-expressing neurons in the mPFC using inhibitory Designer Receptors Activated Only by Designer Drugs (DREADDs). Object- and odor-based IST and DST were then used to assess the effects of acute Cannabis smoke exposure on novelty preference. High-THC but not high-CBD Cannabis smoke exposure impaired novelty preference for objects in the DST. Odor-based novelty recognition deficits were observed in the IST and DST following high-THC smoke exposure but not high -CBD smoke exposure. Lastly, well-established operant conditioning tests for working memory (trial-unique, delayed non-matching-to-location (TUNL) task) and attention (5-choice serial reaction time task (5-CSRTT)) were used to evaluate the effects of acute Cannabis smoke exposure. TUNL task performance was significantly impaired following acute high-THC smoke exposure or intraperitoneal THC injections, but not following low-THC smoke exposure, suggesting that acute exposure to high-THC Cannabis may impact working memory. Neither high-THC or high-CBD acute Cannabis smoke exposure or injected THC impacted performance on the 5-CSRTT. This work demonstrates that high-THC Cannabis exposure impacts short-term memory processes in a manner dependent on the stimulus and memory load(s) and emphasizes the importance of using valid rodent models to study short-term memory. Future directions will include investigating the specific mPFC projections that enable novelty recognition in the odor-based recognition memory tests. As well, the effects of acute Cannabis exposure on mPFC activity during the odor-based recognition memory tests will be examined to understand THC’s action at cannabinoid receptors in the mPFC.
Description
Keywords
Short-term memory, acute Cannabis exposure, rat model
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Anatomy, Physiology, and Pharmacology
Program
Physiology