Biology subjects

Chandler, D. J.

Publications and source records attributed to Chandler, D. J..

3 recordsLinked to original sources

bioRxiv2025

Effects of acute adolescent stress on the acquisition and maintenance of intravenous oxycodone self-administration in male and female rats

BackgroundThe persistent threat of the opioid epidemic warrants investigation into risk factors that predispose individuals to opioid use disorder (OUD). Adolescent stress has been linked to enhanced risk for OUD in humans, however attempts to model this preclinically have yielded mixed results. Additionally, few studies have explored whether adolescent stress modulates the reinforcing effects of prescription opioids. Here we investigate the impact of acute adolescent stress on oxycodone self-administration in male and female rats. MethodsAdolescent male and female rats underwent acute restraint stress during concurrent exposure to predator odor, or control handling. Approximately one week later, subjects were allowed to acquire IV oxycodone self-administration (0.03 mg/kg/inf) over 10 sessions (2 h/day) under a fixed-ratio 1 (FR1) schedule of reinforcement. Following three additional FR1 sessions and seven sessions under FR3, rats underwent two progressive-ratio tests (0.03 mg/kg/inf and 0.06 mg/kg/inf, respectively). Separate groups of adolescent rats underwent similar experimental manipulations but were trained on sucrose reinforcement. ResultsAdolescent stress did not affect the rate of acquisition of IV oxycodone self-administration. However, oxycodone self-administration escalated during post-acquisition FR1 sessions and remained elevated during FR3 sessions in stressed rats as compared to unstressed controls. Adolescent stress exposure did not affect responding during progressive-ratio tests, nor did it affect any measure of sucrose pellet reinforcement. ConclusionsThe present results are the first to demonstrate adolescent stress-induced enhancement of oxycodone reinforcement in rats and provide a preclinical model for investigating the neurobiological mechanisms by which adolescent stress increases vulnerability for prescription opioid misuse.

neuroscience↗

bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

neuroscience↗

bioRxiv2020

Age- and sex- dependent changes in locus coeruleus physiology and anxiety-like behavior in response to acute stress

Adolescence is a critical period of development with increased sensitivity toward psychological stressors. Many psychiatric conditions emerge during adolescence and animal studies have shown that that acute stress has long-term effects on hypothalamic pituitary adrenal axis function and behavior. We recently demonstrated that acute stress produces long-term electrophysiological changes in locus coeruleus and long-lasting anxiety-like behavior in adolescent male rats. Based on prior reports of increased stress sensitivity during adolescence and increased sensitivity of female locus coeruleus toward corticotropin releasing factor, we hypothesized that the same acute stressor would cause different behavioral and physiological responses in adolescent female and adult male rats one week after stressor exposure. In this study, we assessed age and sex differences in how an acute psychological stressor affects corticosterone release, anxiety-like behavior, and locus coeruleus physiology at short- and long-term intervals. All groups of animals responded to stress with elevated corticosterone levels at the acute time point. One week after stressor exposure, adolescent females showed decreased firing of locus coeruleus neurons upon current injection and increased exploratory behavior compared to controls. The results were in direct contrast to changes observed in adolescent males, which showed increased anxiety-like behavior and increased spontaneous and induced firing locus coeruleus neurons a week after stressor exposure. Adult males were both behaviorally and electrophysiologically resilient to the long-term effects of acute stress. Therefore, there may be a normal developmental trajectory for locus coeruleus neurons which promotes stress resilience in adults, but stressor exposure during adolescence perturbs their function. Furthermore, while locus coeruleus neurons are more sensitive to stressor exposure during adolescence, the effect varies between adolescent males and females. These findings suggest that endocrine, behavioral, and physiological responses to stress vary among animals of different age and sex, and therefore these variables should be taken into account when selecting models and designing experiments to investigate the effects of stress. These differences in animals may also allude to age and sex differences in the prevalence of various psychiatric illnesses within the human population.

neuroscience↗