Biology subjects

Laprairie, R. B.

Publications and source records attributed to Laprairie, R. B..

4 recordsLinked to original sources

bioRxiv2023

Characterization of cannabinoid plasma concentration, maternal health, and cytokine levels in a rat model of prenatal Cannabis smoke exposure

Cannabis sativa has gained popularity as a "natural substance", leading many to falsely assume that it is not harmful. This assumption has been documented amongst pregnant mothers, many of whom consider Cannabis use during pregnancy as benign. The purpose of this study was to validate a Cannabis smoke exposure model in pregnant rats by determining the plasma levels of cannabinoids and associated metabolites in the dams after exposure to either Cannabis smoke or injected cannabinoids. Maternal and fetal cytokine and chemokine profiles were also assessed after exposure. Pregnant Sprague-Dawley rats were treated daily from gestational day 6 - 20 with either room air, i.p. vehicle, inhaled high-{Delta}9-tetrahydrocannabinol (THC) (17.98% THC, 0.1% cannabidiol [CBD]) smoke, inhaled high-CBD (0.1% THC, 12.83% CBD) smoke, 3 mg/kg i.p. THC, or 10 mg/kg i.p. CBD. Our data reveal that THC and CBD, but not their metabolites, accumulate in maternal plasma after repeated exposures. Injection of THC or CBD was associated with fewer offspring and increased uterine reabsorption events. For cytokines and chemokines, injection of THC or CBD up-regulated several pro-inflammatory cytokines compared to control or high-THC smoke or high-CBD smoke in placental and fetal brain tissue, whereas smoke exposure was generally associated with reduced cytokine and chemokine concentrations in placental and fetal brain tissue compared to controls. These results support existing, but limited, knowledge on how different routes of administration contribute to inconsistent manifestations of cannabinoid-mediated effects on pregnancy. Smoked Cannabis is still the most common means of human consumption, and more preclinical investigation is needed to determine the effects of smoke inhalation on developmental and behavioural trajectories.

pharmacology and toxicology↗

bioRxiv2023

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

Working memory (WM) is an executive function that orchestrates the use of a limited amount of information, referred to as working memory capacity (WMC), in cognitive functions. In humans, Cannabis exposure impairs WM; however, it is unclear if Cannabis facilitates or impairs rodent WM. Existing literature also fails to address the effects of Cannabis exposure on rodent WMC using exposure paradigms that closely mirror patterns of human use. In the present study, WMC of rats was inferred by novelty preference after a short delay in spontaneous recognition-based tests. Either object or odor-based stimuli were used in different variations of the tests that present identical (IOT) and different (DOT) sets of stimuli (3 or 6) for low-and high-cognitive loads, respectively. Additionally, we present a human-machine hybrid (HYB) behavioral quantification approach which supplements stopwatch-based scoring with supervised machine learning (SML)-based classification, enabling behavioral data to be made publicly available. After validating the spontaneous tests, 6-item IOT and DOT tests with the HYB method were used to evaluate the impact of acute exposure to high-THC or high-CBD Cannabis smoke on novelty preference. Under control conditions, 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-cognitive load. Odor-based recognition deficits were seen under both low-, and high-cognitive loads only following high-THC smoke exposure. Ultimately, these data show that Cannabis smoke exposure impacts novelty preference in a load-dependent, and stimuli-specific manner. Significance StatementWorking memory (WM) capacity is the limited amount of information that can be utilized by WM to orchestrate processes like learning and memory. Using object-and odor-based spontaneous recognition tests, the impact of high-THC or high-CBD Cannabis smoke on novelty preference was evaluated. Behavioral measurements were generated using a combination of open-source analysis software and traditional stopwatch scoring to form a human-machine hybrid (HYB) scoring method. We show novelty preference deficits under high-cognitive loads in object-based tests, while impacting novelty preference under both high-and low-cognitive loads in the odor-based tests. Ultimately, we show that Cannabis smoke exposure affects cognitive functions that underly WM in rats, which has broad implications for human use.

neuroscience↗

bioRxiv2023

Repeated exposure to high-THC Cannabis smoke during gestation alters sex ratio, behavior, and amygdala gene expression of Sprague Dawley rat offspring

Due to the recent legalization of Cannabis in many jurisdictions and the consistent trend of increasing THC content in Cannabis products, there is an urgent need to understand the impact of Cannabis use during pregnancy on fetal neurodevelopment and behavior. To this end, we repeatedly exposed female Sprague-Dawley rats to Cannabis smoke from gestational days 6 to 20 (n=12; Aphria Mohawk; 19.51% THC, <0.07% cannabidiol) or room-air as a control (n=10) using a commercially available system. Maternal reproductive parameters, behavior of the adult offspring, and gene expression in the offspring amygdala were assessed. Body temperature was decreased in dams following smoke exposure and more fecal boli were observed in the chambers before and after smoke exposure in those dams exposed to smoke. Maternal weight gain, food intake, gestational length, litter number, and litter weight were not altered by exposure to Cannabis smoke. A significant increase in the male-to-female ratio was noted in the Cannabis-exposed litters. In adulthood, both male and female Cannabis smoke-exposed offspring explored the inner zone of an open field significantly less than control offspring. Gestational Cannabis smoke exposure did not affect behavior on the elevated plus maze test or social interaction test in the offspring. Cannabis offspring were better at visual pairwise discrimination and reversal learning tasks conducted in touchscreen-equipped operant conditioning chambers. Analysis of gene expression in the adult amygdala using RNAseq revealed subtle changes in genes related to development, cellular function, and nervous system disease in a subset of the male offspring. These results demonstrate that repeated exposure to high-THC Cannabis smoke during gestation alters maternal physiological parameters, sex ratio, and anxiety-like behaviors in the adulthood offspring. Significance statementCannabis use by pregnant women has increased alongside increased THC content in recent years. As smoking Cannabis is the most common method of use, we used a validated model of Cannabis smoke exposure to repeatedly expose pregnant rats to combusted high-THC Cannabis smoke. Our results show alterations in litter sex ratio, anxiety-like behavior, and decision making in the offspring which may relate to subtle changes in expression of amygdala genes related to development, cellular function, and nervous system disease. Thus, we believe this gestational Cannabis exposure model may be useful in delineating long-term effects on the offspring.

neuroscience↗

bioRxiv2022

Sex-specific differences in rotarod performance and type 1 cannabinoid receptor levels in a rat model of traumatic brain injury treated with {triangleup}9-tetrahydrocannabinol

Traumatic brain injuries (TBI) remain one of the leading causes of death and disability world-wide. One emerging area of TBI research is the involvement of the endocannabinoid system (ECS) in response to TBI. Endogenous cannabinoids modulate inflammation, pain, anxiety, and neurotransmitter release through the activation of the cannabinoid receptors CB1R and CB2R. CB1R and CB2R are activated by exogenous cannabinoids such as {Delta}9-tetrahydrocannabinol (THC) found in Cannabis sativa. As public perceptions change in the wake of Cannabis legalization, research into the potential harmful and therapeutic effects of THC following TBI deserve exploration. In this preliminary study, we investigated sex differences in behavioral effects, CB1R abundance, and cytokine profiles in a rat model of moderate TBI treated with 1 mg{middle dot}kg-1 THC (i.p.). Neither TBI nor THC treatment altered catalepsy, body temperature, nociception, or spontaneous alternation as measured in the y-maze. TBI reduced male rotarod performance in both vehicle and THC-treated groups, and THC treatment decreased performance in Sham-TBI rats when compared to vehicle controls. Female rats that received a TBI and THC exhibited lower relative CB1R density when compared to the Sham-TBI+THC group. TBI was associated with reduced interleukin-4 in males; THC increased interleukin-6 in TBI males compared to Sham-TBI. These preliminary results highlight fundamental sex differences in the response of the ECS following TBI. Our results indicate the need for further investigation of the ECS and phytocannabinoids post-TBI in both acute and chronic phases. Significance StatementThe endogenous cannabinoid system is a potential target in the pathophysiology and treatment of traumatic brain injury (TBI). In this study we observed TBI reduced rotarod performance in male rats only and performance was not affected by THC. Female rats the received THC and TBI displayed lower cortical cannabinoid receptor 1 levels. These early results showcase sex differences in rodent models of TBI and the endogenous cannabinoid system.

neuroscience↗