Biology subjects

Baglot, S. L.

Publications and source records attributed to Baglot, S. L..

4 recordsLinked to original sources

bioRxiv2023

Prenatal exposure to THC vapor influences feeding, bodyweight and glucose metabolism under both basal conditions and following high fat diet

4-20% of people report using cannabis during pregnancy, thereby it is essential to assess the associated risks. There is some evidence that prenatal cannabis exposure (PCE) may be associated with increased risk for development of obesity and diabetes later in life, however this has not been well explored under controlled conditions. The aim of this study was to use a translational THC vapor model in rodents to characterize the effects of PCE on adiposity, glucose metabolism, and feeding patterns in adulthood, with focus on potential sex differences. Pregnant Sprague Dawley rats were exposed to vaporized THC (100mg/ml) or control (polyethylene glycol vehicle) across the entire gestational period. Adult offspring from PCE or control litters were subjected to measures of adiposity, glucose metabolism and feeding behavior. Rats were then placed onto special diets (60% high-fat diet [HFD] or control 10% low fat diet [LFD]) for 4-months, then re-subjected to adiposity, glucose metabolism and feeding behavior measurements. PCE did not influence maternal weight or food consumption but was associated with transient decreased pup weight. PCE did not initially influence bodyweight or adiposity, but PCE did significantly reduce the rate of bodyweight gain when animals were maintained on special diets (HFD/LFD), regardless of which diet. Further, PCE had complex effects on glucose metabolism and feeding behavior that were both sex and diet dependent. No effects of PCE were found on plasma leptin or insulin, or white adipose tissue mass. Overall, this data enhances current understanding of the potential impacts of PCE.

neuroscience↗

bioRxiv2022

Characterising the munchies; effects of delta-9-tetrahydrocannabinol (THC) vapour inhalation on feeding patterns, satiety, and macronutrient-specific food preference in male and female rats

With approximately 4% of the worlds population using cannabis, there is need to fully understand how cannabis impacts our health. It is universally known that increased food intake is a side effect of cannabis use, also known as the munchies, and it has been established that delta-9-tetrahydrocannabinol (THC), the major psychoactive cannabinoid in cannabis, drives these feeding effects. These appetitive effects of cannabis or THC have been modeled in humans and rodents but have not been fully explored. Therefore, the aim of this study was to use a translational pre-clinical model to characterise how inhalation of vapour from a THC-dominant cannabis extract alters daily feeding patterns and macronutrient-specific food preferences, with focus on microstructural feeding pattern analysis and potential sex differences. We exposed adult male and female Sprague-Dawley rats to THC-dominant cannabis vapour or vehicle vapour daily, then gave rats access to different foods (chow, high-carbohydrate, and/or high-fat food) and post-vapour feeding patterns measured. To study macronutrient-specific food preferences, rats were given a post-vapour choice between a high-carbohydrate and a high-fat food. To assess satiety, rats were given pre-vapour access to a palatable preload in which they readily consume to become satiated. For some animals, blood and brain samples were collected post-vapour to measure phytocannabinoid and metabolite levels using mass spectrometry. We show that THC vapour inhalation increases food intake in the first hour after vapour exposure, an effect that is not dependent on food type, sex or whether animals are satiated or not. These feeding effects were a result of THC vapour decreasing feeding latency and increasing feeding bout frequency. Consistently, these acute feeding effects were compensated for through reductions in subsequent food intake, and THC vapour did not promote weight gain. THC also altered macronutrient-specific food preferences, increasing high-fat food preference in standard conditions, and increasing high-carbohydrate food preference in satiated conditions so that rats no longer significantly preferred one food over the other. Following vapour exposure, female rats had higher THC and metabolite concentrations in plasma and the hypothalamus than males and showed a stronger high-fat food preference following THC vapour compared to males when given a food choice. Overall, this study complements and builds upon previous clinical and pre-clinical data to fully characterise the effects of THC inhalation on feeding patterns and is the first to directly examine how THC alters macronutrient-specific food preferences and assess if appetitive THC-driven sex differences exist. This research sheds light on whether cannabis use can have energy-balance effects, information which is beneficial for recreational and medical cannabis users.

animal behavior and cognition↗

bioRxiv2021

Pharmacokinetics and Central Accumulation of Delta-9-Tetrahydrocannabinol (THC) and its Bioactive Metabolites are Influenced by Route of Administration and Sex

Up to a third of North Americans over 16 years old report using cannabis in the prior month, most commonly through inhalation. Animal models that reflect human cannabis consumption are critical to study its impacts on brain and behaviour. Nevertheless, most animal studies to date examine effects of cannabis through injection of delta-9-tetrahydrocannabinol (THC; primary psychoactive component of cannabis). THC injections produce markedly different physiological and behavioural effects than inhalation, likely due to distinctive pharmacokinetics of each administration route. The current study directly examined if administration route (injection versus inhalation), with dosing being matched on peak THC blood levels, alters the metabolism of THC, and the central accumulation of THC and its metabolites over time. Adult male and female Sprague-Dawley rats received either a single intraperitoneal injection of THC (2.5 mg/kg) or a single (15 min) session of inhaled exposure to THC distillate (100 mg/mL) vapour. Blood and brains were collected at 15, 30, 60, 90 and 240 minutes post-exposure for analysis of THC and metabolites through mass spectrometry-liquid chromatography. Inhalation results in immediate hypothermia, whereas injection results in delayed hypothermia. Despite achieving comparable peak concentrations of blood THC in both groups, our results indicate higher initial brain THC concentration following inhalation, whereas injection resulted in dramatically higher 11-OH-THC concentrations, a potent THC metabolite, in blood and brain that increased over time. Our results provide evidence that THC and its metabolites exhibit different pharmacokinetic profiles following inhalation versus injection, which could have significant impacts for data interpretation and generalizability. Accordingly, we suggest that translational work in the realm of THC and cannabis strongly consider using inhalation models over those that employ injection. HighlightsO_LIBody temperature as well as blood and brain levels of THC and metabolites differ based on administration route C_LIO_LITHC inhalation results in immediate hypothermia, whereas THC injection results in delayed hypothermia C_LIO_LITHC inhalation results in higher initial brain THC levels than injection C_LIO_LITHC injection results in higher blood & brain 11-OH-THC levels than inhalation C_LIO_LITranslational cannabis work should strongly consider using inhalation over injection C_LI

neuroscience↗

bioRxiv2019

Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats

Recent trends in cannabis legalization have increased the necessity to better understand the effects of cannabis use. Animal models involving traditional cannabinoid self-administration approaches have been notoriously difficult to establish and differences in the drug employed and its route of administration have limited the translational value of preclinical studies. To address this challenge in the field, we have developed a novel method of cannabis self-administration using response-contingent delivery of vaporized {Delta}9-tetrahydrocannabinol-rich (CANTHC) or cannabidiol-rich (CANCBD) complete cannabis extracts. Male Sprague Dawley rats were trained to nosepoke for discrete puffs of CANTHC, CANCBD, or vehicle (VEH) in daily one-hour sessions. Cannabis vapor reinforcement resulted in strong discrimination between active and inactive operanda. CANTHC maintained higher response rates under fixed ratio schedules and higher break points under progressive ratio schedules compared to CANCBD or VEH, and the number of vapor deliveries positively correlated with plasma THC concentrations. Moreover, metabolic phenotyping studies revealed alterations in locomotor activity, energy expenditure, and daily food intake that are consistent with effects in human cannabis users. Furthermore, both cannabis regimens produced ecologically relevant brain concentrations of THC and CBD and CANTHC administration decreased hippocampal CB1 receptor binding. Removal of CANTHC reinforcement (but not CANCBD) resulted in a robust extinction burst and an increase in cue-induced cannabis-seeking behavior relative to VEH. These data indicate that volitional exposure to THC-rich cannabis vapor has bona fide reinforcing properties and collectively support the utility of the vapor self-administration model for the preclinical assessment of volitional cannabis intake and cannabis-seeking behaviors.

neuroscience↗