The role of clock in ethanol-related behaviors

Angela Renee Ozburn, Edgardo Falcon, Shibani Mukherjee, Andrea Gillman, Rachel Arey, Sade Spencer, Colleen A. McClung

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Mice with a mutation in the Clock gene (ClockΔ19) exhibit increased preference for stimulant rewards and sucrose. They also have an increase in dopaminergic activity in the ventral tegmental area (VTA) and a general increase in glutamatergic tone that might underlie these behaviors. However, it is unclear if their phenotype would extend to a very different class of drug (ethanol), and if so, whether these systems might be involved in their response. Continuous access voluntary ethanol intake was evaluated in ClockΔ19 mutants and wild-type (WT) mice. We found that ClockΔ19 mice exhibited significantly increased ethanol intake in a two-bottle choice paradigm. Interestingly, this effect was more robust in female mice. Moreover, chronic ethanol experience resulted in a long-lasting decrease in VTA Clock expression. To determine the importance of VTA Clock expression in ethanol intake, we knocked down Clock expression in the VTA of WT mice via RNA interference. We found that reducing Clock expression in the VTA resulted in significantly increased ethanol intake similar to the ClockΔ19 mice. Interestingly, we also discovered that ClockΔ19 mice exhibit significantly augmented responses to the sedative effects of ethanol and ketamine, but not pentobarbital. However, their drinking behavior was not affected by acamprosate, an FDA-approved drug for the treatment of alcoholism, suggesting that their increased glutamatergic tone might underlie the increased sensitivity to the sedative/hypnotic properties of ethanol but not the rewarding properties of ethanol. Taken together, we have identified a significant role for Clock in the VTA as a negative regulator of ethanol intake and implicate the VTA dopamine system in this response.

Original languageEnglish (US)
Pages (from-to)2393-2400
Number of pages8
JournalNeuropsychopharmacology
Volume38
Issue number12
DOIs
StatePublished - Nov 2013

Fingerprint

Ventral Tegmental Area
Ethanol
Hypnotics and Sedatives
Drinking Behavior
Ketamine
Pentobarbital
RNA Interference
Reward
Pharmaceutical Preparations
Alcoholism
Sucrose
Dopamine
Phenotype
Mutation
Genes

Keywords

  • alcohol preference or consumption
  • circadian
  • Clock gene

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Ozburn, A. R., Falcon, E., Mukherjee, S., Gillman, A., Arey, R., Spencer, S., & McClung, C. A. (2013). The role of clock in ethanol-related behaviors. Neuropsychopharmacology, 38(12), 2393-2400. https://doi.org/10.1038/npp.2013.138

The role of clock in ethanol-related behaviors. / Ozburn, Angela Renee; Falcon, Edgardo; Mukherjee, Shibani; Gillman, Andrea; Arey, Rachel; Spencer, Sade; McClung, Colleen A.

In: Neuropsychopharmacology, Vol. 38, No. 12, 11.2013, p. 2393-2400.

Research output: Contribution to journalArticle

Ozburn, AR, Falcon, E, Mukherjee, S, Gillman, A, Arey, R, Spencer, S & McClung, CA 2013, 'The role of clock in ethanol-related behaviors', Neuropsychopharmacology, vol. 38, no. 12, pp. 2393-2400. https://doi.org/10.1038/npp.2013.138
Ozburn AR, Falcon E, Mukherjee S, Gillman A, Arey R, Spencer S et al. The role of clock in ethanol-related behaviors. Neuropsychopharmacology. 2013 Nov;38(12):2393-2400. https://doi.org/10.1038/npp.2013.138
Ozburn, Angela Renee ; Falcon, Edgardo ; Mukherjee, Shibani ; Gillman, Andrea ; Arey, Rachel ; Spencer, Sade ; McClung, Colleen A. / The role of clock in ethanol-related behaviors. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 12. pp. 2393-2400.
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