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Drug Alcohol Depend. 2014 Nov 1;144:119-26. doi: 10.1016/j.drugalcdep.2014.08.015. Epub 2014 Aug 29.

The effects of chronic alcohol self-administration on serotonin-1A receptor binding in nonhuman primates.

Author information

1
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States; Department of Medical Physics, University of Wisconsin, Madison, WI, United States. Electronic address: ansel.hillmer@yale.edu.
2
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States; Department of Medical Physics, University of Wisconsin, Madison, WI, United States.
3
Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA, United States; Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, United States.
4
Department of Medical Physics, University of Wisconsin, Madison, WI, United States.
5
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States.
6
Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, United States; Department of Kinesiology, University of Wisconsin, Madison, WI, United States.
7
Department of Psychology, University of Wisconsin, Madison, WI, United States; Department of Psychology, Montana State University, Bozeman, MT, United States.
8
Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI, United States; Department of Kinesiology, University of Wisconsin, Madison, WI, United States; Department of Psychology, University of Wisconsin, Madison, WI, United States.
9
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI, United States; Department of Medical Physics, University of Wisconsin, Madison, WI, United States; Department of Psychiatry, University of Wisconsin, Madison, WI, United States.

Abstract

BACKGROUND:

Previous studies have found interrelationships between the serotonin system and alcohol self-administration. The goal of this work was to directly observe in vivo effects of chronic ethanol self-administration on serotonin 5-HT1A receptor binding with [(18)F]mefway PET neuroimaging in rhesus monkeys. Subjects were first imaged alcohol-naïve and again during chronic ethanol self-administration to quantify changes in 5-HT1A receptor binding.

METHODS:

Fourteen rhesus monkey subjects (10.7-12.8 years) underwent baseline [(18)F]mefway PET scans prior to alcohol exposure. Subjects then drank gradually increasing ethanol doses over four months as an induction period, immediately followed by at least nine months ad libidum ethanol access. A post [(18)F]mefway PET scan was acquired during the final three months of ad libidum ethanol self-administration. 5-HT1A receptor binding was assayed with binding potential (BPND) using the cerebellum as a reference region. Changes in 5-HT1A binding during chronic ethanol self-administration were examined. Relationships of binding metrics with daily ethanol self-administration were also assessed.

RESULTS:

Widespread increases in 5-HT1A binding were observed during chronic ethanol self-administration, independent of the amount of ethanol consumed. A positive correlation between 5-HT1A binding in the raphe nuclei and average daily ethanol self-administration was also observed, indicating that baseline 5-HT1A binding in this region predicted drinking levels.

CONCLUSIONS:

The increase in 5-HT1A binding levels during chronic ethanol self-administration demonstrates an important modulation of the serotonin system due to chronic alcohol exposure. Furthermore, the correlation between 5-HT1A binding in the raphe nuclei and daily ethanol self-administration indicates a relationship between the serotonin system and alcohol self-administration.

KEYWORDS:

5-HT1A; Chronic alcohol self-administration; PET imaging; Rhesus monkey; Serotonin

PMID:
25220896
PMCID:
PMC4253864
DOI:
10.1016/j.drugalcdep.2014.08.015
[Indexed for MEDLINE]
Free PMC Article

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