Biology subjects

Bosse, G. D.

Publications and source records attributed to Bosse, G. D..

4 recordsLinked to original sources

bioRxiv2026

A Novel Single-Fish Assay for Ethanol Self-Administration in Zebrafish

Alcohol use disorder (AUD) is a significant public health concern. In Canada, about 18% of individuals aged 15 or older will meet the clinical criteria for AUD at some point in their lives (CAMH, 2023). Treatment options for AUD are limited, and the high relapse rates highlight the urgent need for innovative methods to study and address AUD. Zebrafish (Danio rerio) is an emerging model for exploring the neurobiological impacts of alcohol. Previous studies have demonstrated that zebrafish respond to the rewarding effects of alcohol, but most research methods rely on passive administration, such as immersion, which does not reflect the typical routes of alcohol intake in humans. We previously showed that zebrafish can learn to self-administer drugs of abuse in small groups and conditioned animals are displaying key features of substance abuse disorders. However, group-based conditioning limits our understanding of individual drug preference and intake profile. In this study, we improved upon our previous design by establishing an individual self-administration protocol to measure voluntary alcohol intake and model alcohol use disorder. In this novel assay, individual adult fish learn to discriminate between two zones to self-administer a 5% ethanol solution. Moreover, animals conditioned in this assay can perform progressive ratio and display signs of withdrawal upon cessation of ethanol intake. These results suggest zebrafish can develop ethanol abuse-like behaviour, providing a powerful platform to study genetic predisposition and screen for therapeutic compounds.

neuroscience↗

bioRxiv2025

Prenatal Polysubstance Exposure Alters Behaviour in Zebrafish Larvae

Substance use during pregnancy has been linked to various adverse outcomes in infants, including congenital disabilities, neurodevelopmental delays, and long-term effects such as learning difficulties. An additional concern is that newborns are often exposed to multiple substances in utero. The biological consequences of such exposure remain largely unknown. Zebrafish offer an exciting alternative to fill this gap and deepen our understanding of the biological impact of prenatal multidrug exposure. We utilized zebrafishs scalability to expose embryos to some of the most commonly used substances: nicotine, alcohol, opioids, and all their possible combinations. After embryonic drug exposure, we conducted a detailed behavioural analysis across three developmental stages. Our results revealed drug-specific outcomes, including both synergistic and antagonistic effects. Furthermore, we identified distinctive effects across development, highlighting potential developmental shifts and individual differences in resilience. Overall, these findings demonstrate that prenatal polydrug exposure results in complex, stage-dependent effects, sometimes antagonistic, which cannot be predicted from single-drug outcomes. Our study emphasizes the value of zebrafish as a model for investigating polydrug interactions and provides a framework for exploring biomarkers of vulnerability and resilience in offspring.

neuroscience↗

bioRxiv2024

Development of sensorimotor responses in larval zebrafish: a comparison between wild-type and GCaMP6s transgenic line

During early development, zebrafish larvae exhibit stereotypical behaviors, which rapidly become more complex. Thus, the generation of mutant transgenic lines that maintain transparency throughout their larval stage and that can be used to record brain activity has offered strategic opportunities to investigate the underlying neural correlates of behavior establishment. However, few studies have documented the behavioral profile of these lines during larval development. Here, we set up a behavioral characterization using diverse stimuli (light and vibration) throughout larval development to compare the responses of a transgenic strain expressing a pan-neuronal calcium indicator (GCaMP6s) with that of a wild-type strain. Interestingly, we report a drastic switch in behavioral responses to light transitions at 11 days post-fertilization (dpf) and to vibration stimuli at 14 dpf in both lines. These data highlight a specific time window of behavioral complexification. Meanwhile, we found no major difference in the maturation of sensorimotor responses between GCaMP6s and wild-type strains. Thus, these results support using GCaMP6s strain in investigating the neural mechanisms underlying the developmental maturation of sensorimotor responses. We observed nevertheless some minor differences that suggest careful attention should be taken when using mutant/transgenic lines for behavioral studies. Highlights- Longitudinal investigation of sensorimotor responses by zebrafish during their larval development - During the second week of development, larval zebrafish switch their motor response to light transition - Pan-neuronal nuclear expression of GCaMP6s has little impact on larval fish response to various stimuli

neuroscience↗

bioRxiv2020

The 5α-reductase inhibitor finasteride reduces opioid self-administration

Opioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify novel potential treatments for OUD, we screened a targeted selection of over 100 drugs, using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride did not interfere with the antinociceptive effect of opioids in rat models of neuropathic pain. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish, in a fashion akin to the effects of finasteride. Our results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new option for this disorder.

neuroscience↗