Journal article
Alcohol sensitivity and tolerance encoding in sleep regulatory circadian neurons in Drosophila
Addiction biology, Vol.28(8), e13304
08/2023
DOI: 10.1111/adb.13304
PMCID: PMC10911855
PMID: 37500483
Abstract
Alcohol tolerance is a simple form of behavioural and neural plasticity that occurs with the first drink. Neural plasticity in tolerance is likely a substrate for longer term adaptations that can lead to alcohol use disorder. Drosophila develop tolerance with characteristics similar to vertebrates, and it is a useful model for determining the molecular and circuit encoding mechanisms in detail. Rapid tolerance, measured after the first alcohol exposure is completely metabolized, is localized to specific brain regions that are not interconnected in an obvious way. We used a forward neuroanatomical screen to identify three new neural sites for rapid tolerance encoding. One of these was composed of two groups of neurons, the DN1a and DN1p glutamatergic neurons, that are part of the Drosophila circadian clock. We localized rapid tolerance to the two DN1a neurons that regulate arousal by light at night, temperature-dependent sleep timing, and night-time sleep. Two clock neurons that regulate evening activity, LNd6 and the 5th LNv, are postsynaptic to the DN1as, and they promote rapid tolerance via the metabotropic glutamate receptor. Thus, rapid tolerance to alcohol overlaps with sleep regulatory neural circuitry, suggesting a mechanistic link.
Details
- Title: Subtitle
- Alcohol sensitivity and tolerance encoding in sleep regulatory circadian neurons in Drosophila
- Creators
- Anthony P Lange (Author) - University of California, MercedFred W Wolf (Author) - University of California, Merced
- Resource Type
- Journal article
- Publication Details
- Addiction biology, Vol.28(8), e13304
- DOI
- 10.1111/adb.13304
- PMID
- 37500483
- PMCID
- PMC10911855
- NLM abbreviation
- Addict Biol
- ISSN
- 1355-6215
- eISSN
- 1369-1600
- Publisher
- Wiley
- Grant note
- National Institute on Alcohol Abuse and Alcoholism: R21AA029178, R21AA028352
ACKNOWLEDGEMENTS We thank members of the Wolf lab for intellectual and editing support. This work was supported by R21 AA029178 and R21/R33 AA028352 (F.W.W).
- Language
- English
- Date published
- 08/2023
- Academic Unit
- Psychiatry; Stead Family Department of Pediatrics
- Record Identifier
- 9984847532702771
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