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Mice lacking adenylyl cyclase type 5 (AC5) show increased ethanol consumption and reduced ethanol sensitivity

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Abstract

Rationale

The adenylyl cyclase (AC)/cAMP system is believed to be a key component in regulating alcohol-drinking behavior. It was reported that adenylyl cyclase-5 (AC5) is expressed widely in the brain, with a preferential concentration in the dorsal striatum and nucleus accumbens, brain regions which are important for addiction and emotion. AC5 has been shown to be an essential mediator of morphine addiction and dopamine receptor function; however, it remains unknown whether or not AC5 plays a role in ethanol preference and sensitivity in animals.

Objective

This work was carried out to determine the role of AC5 in alcohol consumption and the hypnotic response to alcohol using AC5 knockout (KO) mice.

Results

In the test for ethanol preference employing a two-bottle free-choice paradigm, AC5 KO mice showed increased ethanol consumption and preference compared with the wild-type mice. Ethanol-induced hypothermia was weakly reduced in AC5 KO mice. AC5 KO mice exhibited sedation/behavioral sleep to high-dose ethanol, but their responses were greatly suppressed compared with the wild-type mice.

Conclusions

These results suggest that AC5 is an important signaling molecule regulating alcohol sensitivity and preference in animals. These data provide critical information for AC5 activation as a candidate target for the treatment of alcoholism.

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Acknowledgment

This research was supported by a grant (2010K000814) from Brain Research Center, The 21st Century Frontier Research Program of the Ministry of Education, Science and Technology, Republic of Korea.

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Authors and Affiliations

  1. Brain Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea

    Kyoung-Shim Kim

  2. Department of Brain and Cognitive Science, Graduate School, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea

    Hannah Kim & Pyung-Lim Han

  3. Brain Disease Research Institute, Graduate School, Ewha Womans University, Seoul, 120-750, Republic of Korea

    Hannah Kim, In-Sun Baek, Ko-Woon Lee & Pyung-Lim Han

  4. Department of Chemistry of Nano Sciences, Graduate School, Ewha Womans University, Seoul, 120-750, Republic of Korea

    In-Sun Baek, Ko-Woon Lee & Pyung-Lim Han

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  1. Kyoung-Shim Kim
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  2. Hannah Kim
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  3. In-Sun Baek
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  4. Ko-Woon Lee
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  5. Pyung-Lim Han
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Correspondence to Pyung-Lim Han.

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Kim, KS., Kim, H., Baek, IS. et al. Mice lacking adenylyl cyclase type 5 (AC5) show increased ethanol consumption and reduced ethanol sensitivity. Psychopharmacology 215, 391–398 (2011). https://doi.org/10.1007/s00213-010-2143-x

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  • DOI: https://doi.org/10.1007/s00213-010-2143-x

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