Authors and Affiliations: Ian A. Mercado-Suárez*¹, Christian D. Del Valle-Colón¹, Nicolás L. Fuenzalida-Uribe², Alfredo Ghezzi¹ Department of Biology, University of Puerto Rico, Río Piedras, San Juan, PR¹, Institute of Neurobiology, San Juan, PR²

Introduction: Alcohol has been identified as the most abused substance. Unrestrained alcohol consumption can have detrimental effect on neurological, psychological, and behavioral processes which can alter the homeostatic balance of the body and create psychological dependence of the substance. Furthermore, the conservation of the body’s circadian rhythms, such as sleep, become affected as alcohol consumption rises. However, the molecular mechanisms controlling gene expression and neuroadaptations that regulate alcohol-induced behaviors and tolerance are not fully understood. This study focuses on determining the role the voltage gated potassium channel Slowpoke (slo) gene has in alcohol-induced tolerance and the effect on the circadian rhythm of sleep.

Methods: Utilizing a Drosophila model, the aim of the study focuses on the lateral ventral neurons (LNv) that function in the production and release of the neurotransmitter pigment-dispersing factor (PDF) which stabilizes and regulates the sleep-wake cycles. Employing the UAS-Gal4 gene manipulation system and an RNAi targeting sequence to knockdown slo-gene expression in the LNv neurons affecting the regulation of PDF (pdf-Gal4/UAS-slo-RNAi). Age-equivalent adult female flies were used to measure the outcome of this genetic manipulation by utilizing activity monitors in quantitative assessment of the effect it has on sleep and alcohol-induced tolerance.

Results: Slo gene knockdown Drosophila present considerable sleep distortion with an increase in alcohol sensitivity caused by a reduced alcohol tolerance. Also, our data show that flies expressing slo-RNAi into LNv neurons have decreased fraction of time sleeping, suggesting Slo knockdown into LNv plays a role modulating sleep behavior in flies.

Conclusion: Results suggest that the Slo gene is involved alcohol-induced behavior regulation and the development of alcohol tolerance. Results shown in this study can advance and innovate beneficial targets for therapeutic treatment in alcohol-induced behaviors.

Key Words: Slowpoke, Drosophila, alcohol, tolerance, sleep

Acknowledgments:

NIH Grant 5P20GM103642, NIH 5R25GM061151-19, NSF Grant 1736026, NIH Grant  2R25NS080687, NIH Grant P20GM103475, NSF: HDR-2008186, NSF Grant 1633184 and NSF Grant 2131647.