Date of Award
Bachelor of Science (B.S.) in Biochemistry and University Honors
Nucleus accumbens, Binge drinking, Drinking behavior, Neurosciences
Background: Binge drinking is a dangerous pattern of behavior. We previously used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the nucleus accumbens (NAc) to modulate binge drinking. Here, we test whether chronically manipulating NAc activity can produce lasting effects on drinking, the transcriptome, and neuronal morphology.
Methods: High Drinking in the Dark (HDID-1) mice were stereotaxically injected with AAV2 DREADDs or GFP in the NAc and treated with vehicle or clozapine-n-oxide (CNO; 1mg/kg) prior to Drinking in the Dark (DID). We then performed 1) RNA-Seq to identify genes changed with alcohol and rescued by CNO and 2) Golgi-Cox staining to determine whether CNO rescued alcohol-induced changes in neuronal morphology. We tested whether targeting HDAC4 via LMK235 (0, 5, 20mg/kg) could reduce drinking.
Results: Chronically increasing NAc activity (via CNO/hM3Dq) decreased binge-like drinking (e.g. Hdac4 was increased with binge drinking, and ameliorated with CNO). Binge drinking increased neuronal complexity in the NAc, and this effect was not present in mice treated with CNO. Chronic treatment with LMK235 reduced binge-like drinking
Discussion: We used DREADDs to produce lasting reductions on drinking behavior, which ameliorated the effects of alcohol on the transcriptome and neuronal morphology. Further, we were able to target specific molecular pathways altered by alcohol but rescued by excitatory DREADDs using pharmacology to mimic the behavioral effects of DREADDs.
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Pozhidayeva, Dar'ya Y., "The Effects of Chronic Chemogenetic Stimulation of Nucleus Accumbens on Binge Drinking, the Transcriptome, and Neuronal Morphology" (2019). University Honors Theses. Paper 724.