Biology subjects

Roebuck, A. J.

Publications and source records attributed to Roebuck, A. J..

4 recordsLinked to original sources

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↗

bioRxiv2021

Adult neurogenesis mediates forgetting of multiple types of memory in the rat

The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampal dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories. Significance StatementRecent evidence indicates that hippocampal neurogenesis mediates forgetting of older memories and enhances encoding of new memories free of proactive interference. This evidence comes from multiple rodent species, behavioral tasks, and methods of increasing neurogenesis. However, a recent paper by (Kodali et al. 2016) found that voluntary exercise-induced neurogenesis did not cause forgetting in the Morris Water Task in rats. The results call into question whether the phenomenon is a conserved function of neurogenesis across species. In the present study, we show that voluntary running causes robust forgetting in rats in a neurogenesis-dependent manner and that the effect is present across three different behavioral tasks, confirming the existence of the phenomenon in rats and adding to the growing evidence that forgetting is a conserved function of hippocampal neurogenesis.

neuroscience↗

bioRxiv2018

The rat medial prefrontal cortex exhibits flexible neural activity states during the performance of an odor span task

Medial prefrontal cortex (mPFC) activity is fundamental for working memory (WM), attention, and behavioral inhibition; however, a comprehensive understanding of the neural computations underlying these processes is still forthcoming. Towards this goal, neural recordings were obtained from the mPFC of awake, behaving rats performing an odor span task of WM capacity. Neural populations were observed to encode distinct task epochs and the transitions between epochs were accompanied by abrupt shifts in neural activity patterns. Putative pyramidal neuron activity increased significantly earlier in the delay for sessions where rats achieved higher spans. Furthermore, increased putative interneuron activity was only observed at the termination of the delay thus indicating that local processing in inhibitory networks was a unique feature to initiate foraging. During foraging, changes in neural activity patterns associated with the approach to a novel odor, but not familiar odors, were robust. Collectively, these data suggest that distinct mPFC activity states underlie the delay, foraging, and reward epochs of the odor span task. Transitions between these states enable successful performance in dynamic environments placing strong demands on the substrates of working memory.

neuroscience↗