Biology subjects

Skorodumov, I.

Publications and source records attributed to Skorodumov, I..

3 recordsLinked to original sources

bioRxiv2026

Multi-Lab Testing of Early Preclinical Discoveries Identifies Promising Treatments

A fundamental challenge in drug development is the frequent failure of early laboratory research to translate into clinical benefit. One promising solution is to confirm findings from exploratory single-laboratory studies across multiple laboratories before clinical testing. We investigated this approach following the conduct of preclinical multi-laboratory studies across different fields of medicine. For this, we evaluated effect sizes, experimental rigor, and a set of criteria to identify determinants of confirmation success. When tested under increased rigor, only a fraction of multi-laboratory studies confirmed the initial results. The underlying effect size reduction was associated with outcome-relevant experimental differences between exploratory and confirmatory stages. In summary, multi-laboratory studies proved highly informative and served as an effective filter for promising treatments.

scientific communication and education↗

bioRxiv2022

Sex and age specific effects on the development of addiction and compulsive-like drinking in rats

Biological factors are known to influence disease trajectories and treatment effectiveness in alcohol addiction. One important biological factor influencing disease dynamics in alcohol use disorder is sex, as preclinical and clinical evidence suggests that gender influences disease trajectories in subjects with alcohol use disorder. Another critical factor is age at first intoxicating drink, which has been identified as a risk factor for later alcohol binging. Preclinical research allows prospective monitoring of rodents throughout the lifespan, providing very detailed information that cannot be acquired in humans. Lifetime monitoring in rodents can be conducted under highly controlled conditions, during which one can systematically introduce multiple biological and environmental factors that impact behaviors of interest. Here, we used the alcohol deprivation effect (ADE) rat model of alcohol addiction in a computerized drinkometer system to study disease dynamics and transition points of addictive behavior in cohorts of adolescent vs. adult as well as male vs. female rats in direct comparison. Early age of onset of drinking (postnatal day 40) in male rats had surprisingly little impact on the development of drinking behavior and compulsivity (quinine taste adulteration) when compared to rats that started drinking during early adulthood (postnatal day 72). However, female rats showed a stronger resistance to quinine taste adulteration after a history of ADEs, indicative of more pronounced compulsive behavior in females as compared to male rats. Specifically, female rats exhibit during quinine taste adulteration a higher frequency of drinking events and a larger access size, especially from the 20% alcohol solution, resulting in fast intoxication despite taste aversion in a relapse-like situation. Our results suggest that drinking patterns, and specifically solution preference as well as access size, provide a valuable indication into determining compulsive drinking. These findings provide a better understanding of sex and age factors involved in the development of drinking behavior that are important in preclinical development of models of addiction, drug development and exploration options for new treatments.

neuroscience↗

bioRxiv2020

Adverse Social Experiences in Adolescent Rats Results in Persisting Sex-Dependent Effects on Alcohol-Seeking Behavior

BackgroundAccumulating clinical evidence suggests women with prior exposure to adverse childhood experiences are more susceptible to alcohol relapse and other health-related issues. Yet, preclinical studies investigating sex-dependent effects of adolescent adverse social experiences (ASEs) on later alcohol-seeking behavior are lacking. This is mainly due to a lack of valid animal models and a shortage of studies comparing sexes. Therefore, we sought to investigate the sex-dependent effects of ASE on adult alcohol-seeking behavior, locomotion and reward sensitivity in both male and female rats. MethodsWe recently developed a rat model for adolescent peer-rejection which allows us to study the long-term consequences of ASEs. Peer-rejection interferes with adolescent rats ability to engage in adequate and reciprocal play behaviors that result in persistent dysregulation of social and pain-related behavior. Adolescent Wistar rats were reared from postnatal day (pd) 21 to pd 50 either within a group of Fischer 344 rats (ASE) or with Wistar rats (control). Adult male and female rats were tested in the reinstatement paradigm for cue-induced alcohol-seeking behavior, circadian locomotor activity, and sucrose consumption in adulthood long-after the termination of the peer-rejection condition. ResultsPeer-rejection induced persistent sex-dependent changes to cue-induced reinstatement. Females showed an increased reinstatement effect while peer-rejected males demonstrated a decrease. No differences were observed in circadian locomotor activity or reward sensitivity to sucrose. ConclusionsPeer-rejection has lasting sex-dependent consequences on alcohol-seeking behavior without affecting locomotion or sweet reward sensitivity. Our results suggest that peer-rejected female rats represent a vulnerable population to study relapse-like behaviors similar to clinical findings. While males seem to buffer the peer-rejection effect and demonstrate resilience to later-life alcohol-seeking behaviors, measured by the reinstatement effect. Finally, we provide a novel approach to investigate the molecular and neurobiological underpinnings of ASEs on alcohol and other drug-seeking behaviors.

neuroscience↗