Biology subjects

Moore, C. F.

Publications and source records attributed to Moore, C. F..

7 recordsLinked to original sources

bioRxiv2026

Chronic {triangleup}9-Tetrahydrocannabinol Vapor Self-Administration Modulates Gut Microbiota and the Immune and Endocannabinoid Systems in Female Sprague-Dawley Rats

Vaping of cannabis and its primary components, including {triangleup}9-tetrahydrocannabinol (THC), has increased during the last decade, especially among adolescents and adults. While the behavioral consequences of THC, including anxiety, depression, and associated impacts on reward-related signaling, are well documented, evaluation of additional pathways that have implications for neuronal function remains relatively unexplored. Further, despite evidence of the impact of THC on several physiologic processes, most studies have focused on the brain even though the endocannabinoid system with which THC interacts has widespread expression and functions throughout the body. To address these gaps, we obtained biological samples from adult female Sprague-Dawley rats (N=5-6 per group; all females) that were passively exposed to THC or vehicle vapor and then allowed to self-administer vaporized THC or vehicle intermittently for nine months. Animals were euthanized, and brain and peripheral organs were collected for analyses. We evaluated genes of endocannabinoid system-related receptors, modulators, ion channels, and metabolic enzymes, along with immune and microbiome-related pathways in 9 peripheral organs, 14 brain regions, and plasma. We observed that rats exposed to chronic intermittent THC vapor administration had widespread modulation of several endocannabinoid-system genes only in the brain, with most changes occurring in the dorsal striatum and hippocampus. In contrast, endocannabinoid-system gene expression in all evaluated peripheral organs remained unchanged after THC exposure. Similar findings occurred with immune-relevant genes, where il-1beta, il-6, ccl2, and mx1 were modulated only in the brain while expression in peripheral organs remained unchanged. Immune system modulation following chronic THC exposure significantly elevated plasma concentrations of IL-17A, gut microbiota dysbiosis, and global changes to circulating metabolites, including several amino acids, fatty acids, aminosugar, and nucleic acids. Our findings provide, for the first time, a whole-body evaluation of the molecular effects of chronic THC exposure throughout adulthood on the endocannabinoid and immune systems that have implications for cannabinoid-related behavioral effects.

immunology↗

bioRxiv2025

Effects of oral cannabidiol (CBD) on spontaneous opioid withdrawal in male and female rats

Opioid use disorder (OUD) remains a public health crisis in the United States. A key factor in continued use, relapse risk, and overdose is the severe withdrawal syndrome that accompanies abstinence. Observational studies suggest cannabis may improve outcomes for patients with OUD. Cannabidiol (CBD), a non-intoxicating compound found in cannabis, is being investigated as a potential treatment for OUD. This study investigated whether CBD alleviated withdrawal symptoms in a rat model of opioid dependence. Sprague Dawley rats (N = 100, 50% female) were administered escalating doses of morphine across 10 days (10-50 mg/kg, s.c., twice daily). Following abrupt discontinuation, withdrawal outcomes were evaluated across acute (38-hr) and protracted (up to day 7) timepoints. Rats were treated with pure CBD (10 or 30 mg/kg, p.o.) or vehicle (sesame oil; 1 mg/ml) daily, beginning 14-hrs after their final morphine or saline injection (n = 8-9 per sex/group). Withdrawal severity was assessed through physical measurements of body weight, food intake, and somatic signs (e.g., body shakes, diarrhea), and pain sensitivity, as well as measurements of anxiety-like behaviors in the protracted phase. Compared to non-dependent controls, morphine-dependent rats had decreased body weight and food intake, showed greater somatic signs, and had increased pain sensitivity that peaked in acute withdrawal (38-hr). Oral CBD did not affect physical symptoms of opioid withdrawal nor protracted anxiety-like behaviors. These data indicate that CBD alone may have limited effectiveness for treating opioid withdrawal. Reports of improved withdrawal symptoms after cannabis use may be attributed to other compounds in cannabis. Public health significanceThis study suggests that daily oral treatment with pure CBD at doses available to consumers does not improve physical or psychological symptoms of withdrawal from chronic opioids.

pharmacology and toxicology↗

bioRxiv2025

Effects of sex and pre-exposure on Δ9-tetrahydrocannabinol (THC) vapor self-administration in rats

RationaleAnimal models of cannabinoid self-administration are critical for advancing our understanding of the neurobiology of cannabis use and for developing medications for Cannabis Use Disorder. Use of vapor inhalation models have translational relevance, as the majority of human cannabis user do so by inhalation (e.g., smoking, vaporization). MethodsAdult male and female Sprague Dawley rats (N=96, 6-12 per sex/group) were pre-exposed to vaporized THC or vehicle (Veh; 100% propylene glycol). Rats were then trained to self-administer vapor puffs of either THC (50 mg/ml training dose) or Veh under a fixed ratio (FR) 1 schedule. Responding was then assessed under increasing response costs (FR1-5) and different doses (50-200 mg/ml) of THC. As a secondary study aim, we assessed the effects of pre-exposure to THC (or Veh) on self-administration of THC vapor or Veh vapor. ResultsThere were no differences in responding for THC and Veh vapor under an FR1 schedule. As the FR increased, rats increased their responses for THC, and female rats in the THC group responded more than female rats in the Veh vapor group under FR4-5 schedules. When THC concentration was varied, rats titrated their intake in a predictable U-shaped pattern. THC vapor pre-exposure significantly increased self-administration of THC vapor, but not Veh vapor. ConclusionsMale and female rats voluntarily administered THC vapor in a sustained manner across several months, replicating what has been shown with vaporized cannabis extracts male rats. This study is the first to demonstrate that THC vapor has reinforcing properties in female rats and that pre-exposure is critical for engendering higher intake. This is a promising model of voluntary THC vapor administration.

animal behavior and cognition↗

bioRxiv2023

Roadmap for Canonical and Extended Endocannabinoid System Receptors in Peripheral Organs of Preclinical Animal Models

The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold-standard behavioral tests. However, the potential for lack of clinical translation to non-human primates and humans is high as cross-species comparisons of the endocannabinoid system has not been evaluated. To bridge this gap in knowledge, we evaluate the relative gene expression of 14 canonical and extended endocannabinoid receptors in seven peripheral organs of C57/BL6 mice, Sprague-Dawley rats, and non-human primate rhesus macaques. Notably, we identify species- and organ-specific heterogeneity in endocannabinoid receptor distribution where there is surprisingly limited overlap among the preclinical models. Importantly, we determined there were only five receptors (CB2, GPR18, GPR55, TRPV2, and FAAH) that had identical expression patterns in mice, rats, and rhesus macaques. Our findings demonstrate a critical, yet previously unappreciated, contributor to challenges of rigor and reproducibility in the cannabinoid field, which has profound implications in hampering progress in understanding the complexity of the endocannabinoid system and development of cannabinoid-based therapies.

molecular biology↗

bioRxiv2021

Δ9-tetrahydrocannabinol (THC) vapor exposure produces conditioned rewarding effects in male and female rats

BackgroundThe use of place conditioning procedures and drug vapor exposure models can increase our understanding of the rewarding and aversive effects of vaped cannabis products. Currently there are limited data on the conditioned rewarding effects of vaporized {Delta}9-tetrahydrocannabinol (THC), the primary psychoactive constituent of cannabis in rats, and no studies to date examining sex differences. MethodsMale and female Sprague-Dawley rats (N=96; 12 per sex/group) underwent place conditioning sessions immediately after exposure to THC or vehicle (propylene glycol, PG) vapor. Locomotor activity was measured by beam breaks during conditioning sessions. THC vapor-conditioned rats received one of three THC vapor exposure amounts (low: 5 puffs of 100 mg/ml THC, medium: 5 puffs of 200 mg/ml THC, or high: 10 puffs of 200 mg/ml THC) and matched vehicle vapor (PG) exposure on alternate days for 16 daily sessions. A no THC control group of vehicle-conditioned rats received only PG vapor exposure each day. After the 8th and 16th conditioning sessions, untreated rats were tested for conditioned place preference (CPP) or avoidance (CPA). Next, extinction tests and a THC vapor-primed reinstatement test were conducted. ResultsTHC vapor produced CPP and locomotor effects in an exposure dependent manner, and some sex differences were observed. Low THC vapor exposure did not produce CPP in males or females. Medium THC vapor exposure produced CPP in males, but not females. High THC vapor exposure produced CPP in both males and females. Medium and high THC vapor exposure amounts produced hyperactivity in female rats, but not male rats. CPP was more resistant to extinction in females than males. THC vapor re-exposure (i.e., drug-prime) after extinction did not result in reinstatement of CPP for either sex. ConclusionThis study demonstrates conditioned rewarding effects of THC vapor in both male and female rats and provides evidence for sex differences in amounts of THC vapor that produce CPP and in time to extinction. CPA was not observed at any of the THC vapor exposure amounts tested. These data provide a foundation for future exploration of the conditioned effects of cannabis constituents and extracts using vapor exposure models.

animal behavior and cognition↗

bioRxiv2021

Cannabinoid tetrad effects of oral Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in male and female rats: sex, dose-effects and time course evaluations

Rationale The legalization of medicinal use of Cannabis sativa in most US states and the removal of hemp from the Drug Enforcement Agency (DEA) controlled substances act has resulted in a proliferation of products containing {Delta}9-tetrahydrocannabinol (THC) and cannabidiol (CBD) for oral consumption (e.g., edibles, oils and tinctures) that are being used for recreational and medicinal purposes. Objective This study examined the effects of cannabinoids THC and CBD when administered orally on measures of pain sensitivity, body temperature, locomotor activity, and catalepsy (i.e., cannabinoid tetrad) in male and female Sprague Dawley rats. Methods Rats (N=24, 6 per sex/drug group) were administered THC (1-20 mg/kg), CBD (3-30 mg/kg), or sesame oil via oral gavage. Thermal and mechanical pain sensitivity (tail flick assay, von Frey test), rectal measurements for body temperature, locomotor activity, and the bar-test of catalepsy were completed. A separate group of rats (N=8/4 per sex) were administered morphine (5-20 mg/kg; intraperitoneal, IP) and evaluated for pain sensitivity as a positive control. Results We observed classic tetrad effects of antinociception, hypothermia, hyper- and hypolocomotion, and catalepsy after oral administration of THC that were long lasting (>7 hours). CBD modestly increased mechanical pain sensitivity and produced sex-dependent effects on body temperature and locomotor activity. Conclusions Oral THC and CBD produced long lasting effects, that differed in magnitude and time course when compared with other routes of administration. Examination of cannabinoid effects administered via different routes of administration, species, and in both males and females is critical to enhance translation.

pharmacology and toxicology↗

bioRxiv2020

Antinociceptive, hypothermic, and appetitive effects of vaped and injected Δ9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex

Advances in drug vapor exposure systems utilizing e-cigarette technology have enabled evaluation of {Delta}-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Wistar and Sprague Dawley rats (N=22, 5-6/group) received THC via IP injection (1-20 mg/kg) and passive exposure to THC vapor (200 mg/ml; 5 conditions) in a within subject design. The effects of vaped and injected THC were determined using the tail-withdrawal assay for nociception, rectal measurements of body temperature, and progressive-ratio responding for food pellets. Plasma THC concentrations were assessed after 10 mg/kg IP THC or THC vapor. THC produced dose and exposure-dependent antinociception and hypothermia. THC vapor produced inverted U-shaped effects in motivation to obtain food, while IP THC reduced PR breakpoints. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL). THC vapor exposure produces reliable, dose-orderly effects on nociception, body temperature, and food-maintained behavior that is comparable to effects observed after IP THC. There are considerable differences between the time course of behavioral outcomes produced by these two different routes of administration.

animal behavior and cognition↗