DESCRIPTION:

Here, female High Drinking in the Dark (HDID) mice were stereotaxically injected with 0.5uL rAAV2/5-CMV-Cre-GFP and 0.5uL rAAV2-hSyn-DIO-hM3Dq-mCherry bilaterally into the NAc. A Drinking in the Dark (DID) experiment lasting 6 weeks was carried out with 2 fluid groups (water or ethanol) and 2 treatment groups (VEH/VEH/VEH or VEH/CNO/VEH). Mice were serially treated with vehicle prior to DID during week 1 to establish baseline drinking, CNO (1mg/kg) during weeks 2-5 to measure the effects of chronic treatment, and then mice were treated with vehicle again during week 6 to determine if there were any lasting effects of chronic CNO treatment. This gene set comprises 2,377 genes that were differentially expressed in the nucleus accumbens of ethanol drinking HDID mice treated with CNO as compared to the water drinking and vehicle treated control group.

LABEL:

DEGs EtOH(CNO)

SCORE TYPE:

P-Value

DATE ADDED:

2019-07-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Darya Y. Pozhidayeva, Sean P. Farris, Calla M. Goeke, Evan J. Firsick, Kayla G. Townsley, Marina Guizzetti, and Angela R. Ozburn

TITLE:

Chronic chemogenetic stimulation of the nucleus accumbens produces lasting reductions in binge drinking and ameliorates alcohol-related morphological and transcriptional changes

JOURNAL:

None

ABSTRACT:

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 in mice. Here, we test whether chronically manipulating NAc activity can produce lasting effects on drinking, neuronal morphology, and the transcriptome in mice selectively bred to drink to intoxication. Chronically increasing NAc activity (via CNO/hM3Dq) decreased binge-like drinking, an effect lasting at least 7d. CNO did not alter intake in hM4Di- or GFP-expressing mice. Binge drinking increased neuronal complexity in the NAc, an effect which was not present in mice treated with CNO. We observed significant changes in expression of several plasticity-related genes (e.g. Hdac4 was increased with binge drinking, and ameliorated with CNO). Chronic treatment with LMK235, an HDAC4/5 inhibitor, reduced binge-like drinking. Thus, we were able to target specific molecular pathways using pharmacology to mimic the behavioral effects of DREADDs.