@article{huffstetler_cochran_may_maykut_silver_cedeno_franck_cox_fadool_2023, title={Single cannabidiol administration affects anxiety-, obsessive compulsive-, object memory-, and attention-like behaviors in mice in a sex and concentration dependent manner}, url={http://dx.doi.org/10.1016/j.pbb.2022.173498}, DOI={10.1016/j.pbb.2022.173498}, abstractNote={The behavioral effects of cannabidiol (CBD) are understudied, but are important, given its therapeutic potential and widespread use as a natural supplement. The objective of this study was to test whether a single injection of CBD affected anxiety-like or attention-like behavior, or memory in wildtype mice or mice with reported trait anxiety due to a targeted gene-deletion in a voltage-dependent potassium channel, Kv1.3. Wildtype C57BL/6 J and Kv1.3−/− mice of both sexes were reared to adulthood and then administered an intraperitoneal injection of 10 or 20 mg/kg CBD. Mice were behaviorally-phenotyped using the marble-burying test, the light-dark box (LDB), short (1 h) and long-term (24 h) object memory test, the elevated-plus maze (EPM), and the object-based attention task in order to assess obsessive compulsive-, anxiety-, and attention-like behaviors, and memory. We discovered that acute CBD treatment reduced marble burying in male, but not female mice. CBD was effective in lessening anxiety-like behaviors determined by the LDB test in both male and female wildtype mice, whereby the effective dose required to observe the effect in females was less. In Kv1.3−/− mice, CBD increased anxiety-like behaviors in the LDB in both sexes at the higher concentration of CBD and it similarly increased anxiety-like behavior in females in the EPM at the lower concentration of CBD. Long-term object memory was reduced in male wildtype mice at the lower concentration of CBD. Finally, ADHD- or attention-like behaviors were not altered by CBD in wildtype mice, but in Kv1.3−/− mice, females were observed to have a loss in attention while males demonstrated improved attention. We conclude that administration of a single dose of CBD has immediate effects on mouse behavior that is dose, sex, and anxiety-state dependent – and that these behavioral outcomes are important to examine in parallel human trials.}, journal={Pharmacology Biochemistry and Behavior}, author={Huffstetler, Carley Marie and Cochran, Brigitte and May, Camilla Ann and Maykut, Nicholas and Silver, Claudia Rose and Cedeno, Claudia and Franck, Ezabelle and Cox, Alexis and Fadool, Debra Ann}, year={2023}, month={Jan} }
 @article{chelette_loeven_gatlin_conde_huffstetler_qi_fadool_2022, title={Consumption of dietary fat causes loss of olfactory sensory neurons and associated circuitry that is not mitigated by voluntary exercise in mice}, url={https://doi.org/10.1113/JP282112}, DOI={10.1113/JP282112}, abstractNote={Excess nutrition causes loss of olfactory sensory neurons (OSNs) and reduces odour discrimination and odour perception in mice. To separate diet-induced obesity from the consumption of dietary fat, we designed pair-feeding experiments whereby mice were maintained on isocaloric diets for 5 months, which prevented increased fat storage. To test our hypothesis that adiposity was not a prerequisite for loss of OSNs and bulbar projections, we used male and female mice with an odorant receptor-linked genetic reporter (M72tauLacZ; Olfr160) to visualize neural circuitry changes resulting from elevated fat in the diet. Simultaneously we monitored glucose clearance (diagnostic for prediabetes), body fat deposition, ingestive behaviours, select inflammatory markers and energy metabolism. Axonal projections to defined olfactory glomeruli were visualized in whole-mount brains, and the number of OSNs was manually counted across whole olfactory epithelia. After being pair fed a moderately high-fat (MHF) diet, mice of both sexes had body weight, adipose deposits, energy expenditure, respiratory exchange ratios and locomotor activity that were unchanged from control-fed mice. Despite this, they were still found to lose OSNs and associated bulbar projections. Even with unchanged adipocyte storage, pair-fed animals had an elevation in TNF cytokines and an intermediate ability for glucose clearance. Albeit improving health metrics, access to voluntary running while consuming an ad libitum fatty diet still precipitated a loss of OSNs and associated axonal projections for male mice. Our results support that long-term macronutrient imbalance can drive anatomical loss in the olfactory system regardless of total energy expenditure. KEY POINTS: Obesity can disrupt the structure and function of organ systems, including the olfactory system that is important for food selection and satiety. We designed dietary treatments in mice such that mice received fat, but the total calories provided were the same as in control diets so that they would not gain weight or increase adipose tissue. Mice that were not obese but consumed isocaloric fatty diets still lost olfactory neuronal circuits, had fewer numbers of olfactory neurons, had an elevation in inflammatory signals and had an intermediate ability to clear glucose (prediabetes). Mice were allowed access to running wheels while consuming fatty diets, yet still lost olfactory structures. We conclude that a long-term imbalance in nutrition that favours fat in the diet disrupts the olfactory system of mice in the absence of obesity.}, journal={The Journal of Physiology}, author={Chelette, Brandon M. and Loeven, Ashley M. and Gatlin, Destinee N. and Conde, Daniel R. Landi and Huffstetler, Carley M. and Qi, Meizhu and Fadool, Debra Ann}, year={2022}, month={Mar} }