Biology subjects

Chang, S. E.

Publications and source records attributed to Chang, S. E..

9 recordsLinked to original sources

bioRxiv2026

Chronic semaglutide treatment attenuates cue-induced reinstatement of cocaine-seeking and cocaine-induced stereotypy in male and female rats

Following cocaine self-administration, male and female rats received daily semaglutide during a 30-day abstinence period before cue- and cocaine-induced reinstatement tests. Semaglutide attenuated cue-induced reinstatement and cocaine-induced stereotypy, although operant responding was elevated following cocaine priming. These findings support further investigation of semaglutide as a treatment for cocaine use disorder.

neuroscience↗

bioRxiv2026

Differential acquisition of cocaine and heroin self-administration in a rat model of internalizing versus externalizing temperament

Substance Use Disorders (SUDs) constitute a major and rising public health concern. In addition, there is a growing appreciation that different classes of addictive substances are likely to lead to qualitatively different types of SUDs requiring differing treatment and relapse prevention strategies to be most effectively managed. Biological temperament, particularly on the internalizing - externalizing axis, is well established to influence addiction susceptibility. Externalizing behavior has long been understood to predispose individuals to addiction through novelty-seeking, sensation-seeking and impulsivity, while internalizing behavior provides an alternate pathway into addiction via increased occurrence of comorbid disorders (anxiety, depression). Here, we utilize a selectively bred rat model of internalizing vs externalizing temperament (bred High Responders, representing genetically mediated externalizing behavior and bred Low Responders, representing internalizing behavior) to examine differences in the acquisition of self-administration of the prototypical psychostimulant cocaine and the prototypical opioid heroin (diacetylmorphine). We found that, as predicted, cocaine and heroin drove different patterns of acquisition in the two different bred lines of rats. Further, this was influenced by temperament in complex ways. Notably, in females the "telescoping effect" for opioid addiction-like behavior was primarily specific to externalizing temperament. These findings highlight the impact and interaction of many factors, including drug class, temperament, and sex, on the acquisition of drug-taking behavior. Additionally, these findings indicate that sex differences in addiction vulnerability may be influenced in part by biological temperament.

animal behavior and cognition↗

bioRxiv2025

Chronic semaglutide treatment enhances the incentive motivational value of a small food reward and associated cue in male and female rats

RationaleGlucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, are increasingly utilized in clinical practice due to their efficacy in promoting sustained weight loss following chronic administration. While acute treatment with GLP-1 receptor agonists has been shown to suppress food intake and reward-seeking behaviors in rodent models, the impact of prolonged exposure on preclinical measures of motivated behavior remains insufficiently characterized. ObjectivesThis study aimed to systematically evaluate the effects of chronic administration of semaglutide on both the acquisition and expression phases of Pavlovian conditioned approach (PavCA)--a behavioral paradigm used to assess the attribution of incentive salience to a food-paired cue. The influence of chronic semaglutide on the conditioned reinforcing properties of the food-associated cue, performance on a progressive ratio (PR) schedule for food reward, and ad libitum consumption of the food reward were also assessed. ResultsChronic semaglutide administration did not significantly alter either the acquisition or the expression of PavCA behavior. However, relative to vehicle-treated controls, semaglutide markedly enhanced responding for the food-associated cue during a conditioned reinforcement test and increased PR responding for the food reward. In contrast, semaglutide reduced both free consumption of the food reward and homecage chow intake. ConclusionsThese findings demonstrate that chronic semaglutide administration potentiates the incentive value of food-paired cues and increases motivation for food reward under restricted access conditions, yet attenuates overall food consumption when food is freely available. This dissociation highlights the nuanced effects of semaglutide on motivated behavior and suggests an amplification of the reinforcing properties of discrete, limited food rewards and associated cues.

neuroscience↗

bioRxiv2025

Precision functional mapping reveals less inter-individual variability in the child vs. adult human brain

Human brain organization shares a common underlying structure, though recent studies have shown that features of this organization also differ significantly across individual adults. Understanding the developmental pathways that lead to individually unique brains is important for advancing models of cognitive development and neurodevelopmental disorders. Here we use highly personalized precision neuroimaging methods to map brain networks within 12 individual children, ages 8-12 years. We demonstrate fMRI functional connectivity maps that substantially exceed the reliability of traditional techniques, allowing us to measure individual differences after overcoming biases from measurement noise. Children share core functional network topography, with greatest inter-individual variability in association regions, consistent with adult findings. However, children show less between-subject variability than adults, suggesting increasing individual differentiation in brain networks with development. This pediatric precision neuroimaging dataset is publicly available to support future brain development research and provides a high-fidelity foundation for studying individual variation in atypical development.

neuroscience↗

bioRxiv2024

Unique functional neuroimaging signatures of genetic versus clinical high risk for psychosis

Background22q11.2 Deletion Syndrome (22qDel) is a copy number variant (CNV) associated with psychosis and other neurodevelopmental disorders. Adolescents at clinical high risk for psychosis (CHR) have subthreshold psychosis symptoms without known genetic risk factors. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped results to biological pathways. MethodsWe analyzed two large multi-site cohorts with resting-state functional MRI (rs-fMRI): 1) 22qDel (n=164, 47% female) and typically developing (TD) controls (n=134, 56% female); 2) CHR individuals (n=244, 41% female) and TD controls (n=151, 46% female) from the North American Prodrome Longitudinal Study-2. We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions, testing case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation. ResultsBSV, LC, and GBC are significantly disrupted in 22qDel compared with TD controls (False Discovery Rate q<0.05). Spatial maps of BSV and LC differences are highly correlated with each other, unlike GBC. In CHR, only LC is significantly altered versus controls, with a different spatial pattern compared to 22qDel. Group differences map onto biological gradients, with 22qDel effects strongest in regions with high predicted blood flow and metabolism. Conclusion22qDel and CHR exhibit divergent effects on fMRI temporal variability and multi-scale functional connectivity. In 22qDel, strong and convergent disruptions in BSV and LC not seen in CHR individuals suggest distinct functional brain alterations.

neuroscience↗

bioRxiv2024

The effect of corticosterone on the acquisition of Pavlovian conditioned approach behavior is dependent on sex and vendor

Cues in the environment become predictors of biologically relevant stimuli, such as food, through associative learning. These cues can not only act as predictors but can also be attributed with incentive motivational value and gain control over behavior. When a cue is imbued with incentive salience, it attains the ability to elicit maladaptive behaviors characteristic of psychopathology. We can capture the propensity to attribute incentive salience to a reward cue in rats using a Pavlovian conditioned approach paradigm, in which the presentation of a discrete lever-cue is followed by the delivery of a food reward. Upon learning the cue-reward relationship, some rats, termed sign-trackers, develop a conditioned response directed towards the lever-cue; whereas others, termed goal-trackers, approach the food cup upon lever-cue presentation. Here, we assessed the effects of systemic corticosterone (CORT) on the acquisition and expression of sign- and goal-tracking behaviors in male and female rats, while examining the role of the vendor (Charles River or Taconic) from which the rats originated in these effects. Male and female rats from Charles River had a greater tendency to sign-track than those from Taconic. Administration of CORT enhanced the acquisition of sign-tracking behavior in males from Charles River and females from both vendors. Conversely, administration of CORT had no effect on the expression of the conditioned response. These findings demonstrate a role for CORT in cue-reward learning and suggest that inherent tendencies towards sign- or goal-tracking may interact with this physiological mediator of motivated behavior. HighlightsO_LIMale and female rats from Charles River exhibit more sign-tracking relative to those from Taconic. C_LIO_LICorticosterone increases the acquisition of sign-tracking in male rats from Charles River. C_LIO_LICorticosterone increases the acquisition of sign-tracking in female rats, regardless of vendor. C_LIO_LIThere is no effect of corticosterone on the expression of sign-tracking behavior in either male or female rats. C_LI

neuroscience↗

bioRxiv2022

XIST ribonucleoproteins promote female sex-biased autoimmunity

Autoimmune diseases disproportionately affect females more than males. The XX sex chromosome complement is strongly associated with susceptibility to autoimmunity. Xist long noncoding RNA (lncRNA) is expressed only in females to randomly inactivate one of the two X chromosomes to achieve gene dosage compensation. Here, we show that the Xist ribonucleoprotein (RNP) complex, comprised of numerous autoantigenic components, is an important driver of sex-biased autoimmunity. Inducible transgenic expression of a non-silencing form of Xist in male mice introduced Xist RNP complexes and sufficed to produce autoantibodies. Male SJL/J mice expressing transgenic Xist developed more severe multiorgan pathology in pristane-induced model of lupus than wild-type males. Xist expression in males reprogrammed T and B cell population and chromatin states to more resemble wild type females. Human patients with autoimmune diseases displayed significant autoantibodies to multiple components of XIST RNP. Thus, a sex-specific lncRNA scaffolds ubiquitous RNP components to drive sex-biased immunity. HIGHLIGHTSO_LITransgenic mouse models inducibly express Xist in male animals. C_LIO_LIXist expression in males induce autoantibodies and autoimmune pathology. C_LIO_LIXist in males reprograms T and B cell populations to female-like patterns. C_LIO_LIAutoantibodies to Xist RNP characterize female-biased autoimmune diseases. C_LI

molecular biology↗

bioRxiv2022

Variability in cognitive task performance in early adolescence is associated with stronger between-network anticorrelation and future attention problems

BackgroundIntra-individual variability (IIV) during cognitive task performance is a key behavioral index of attention and consistent marker of ADHD. In adults, lower IIV has been associated with anticorrelation between the default mode network (DMN) and dorsal attention network (DAN) - thought to underlie effective allocation of attention. However, whether these behavioral and neural markers of attention are (i) associated with each other and (ii) can predict future attention-related deficits has not been examined in a developmental, population-based cohort. MethodsWe examined relationships at the baseline visit between IIV on three cognitive tasks, DMN-DAN anticorrelation, and parent-reported attention problems using the Adolescent Brain and Cognitive Development Study (n=11,878 participants, aged 9-10, female=47.8%). We also investigated whether behavioral and neural markers of attention at baseline predicted attention problems, 1, 2, and 3 years later. ResultsAt baseline, greater DMN-DAN anticorrelation was associated with lower IIV across all three cognitive tasks (unstandardized {beta}: 0.22-0.25). Older age at baseline was associated with stronger DMN-DAN anticorrelation and lower IIV ({beta}: -0.005--0.0004). Weaker DMN-DAN anticorrelation and IIV were cross-sectionally associated with attention problems ({beta}: 1.41-7.63). Longitudinally, lower IIV at baseline was associated with less severe attention problems, 1-3 years later, after accounting for baseline attention problems ({beta}: 0.288-0.77). ConclusionsThe results suggest that IIV in early adolescence is associated with worsening attention problems in a representative cohort of US youth. Attention deficits in early adolescence may be important for understanding and predicting future cognitive and clinical outcomes.

neuroscience↗

bioRxiv2020

Inhibition of a cortico-thalamic circuit attenuates cue-induced reinstatement of drug-seeking behavior in relapse prone rats

Relapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether "top-down" cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype - locomotor response to novelty - inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is driven by individual differences in the propensity to attribute incentive salience to discrete reward cues.

neuroscience↗