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Drug Alcohol Depend. 2014 May 1;138:216-9. doi: 10.1016/j.drugalcdep.2014.01.027. Epub 2014 Feb 15.

Changes in the α4β2* nicotinic acetylcholine system during chronic controlled alcohol exposure in nonhuman primates.

Author information

  • 1Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, United States; Department of Medical Physics, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI 53705, United States. Electronic address: ahillmer@wisc.edu.
  • 2Department of Internal Medicine, University of Pittsburgh, Pittsburgh, PA United States; Department of Biostatistics, University of Pittsburgh, 200 Meyran Avenue, Pittsburgh, PA 15213, United States.
  • 3Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, United States; Department of Medical Physics, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI 53705, United States.
  • 4Department of Medical Physics, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI 53705, United States.
  • 5Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, United States.
  • 6Harlow Center for Biological Psychology, University of Wisconsin, Madison, 22 North Charter Street, Madison, WI 53715, United States; Department of Kinesiology, University of Wisconsin, Madison, 2000 Observatory Drive, Madison, WI 53706, United States.
  • 7Department of Psychology, University of Wisconsin, Madison, 1202 W. Johnson Street, Madison, WI 53706, United States; Department of Psychology, Montana State University, P.O. Box 173440, Bozeman, MT 59717, United States.
  • 8Harlow Center for Biological Psychology, University of Wisconsin, Madison, 22 North Charter Street, Madison, WI 53715, United States; Department of Kinesiology, University of Wisconsin, Madison, 2000 Observatory Drive, Madison, WI 53706, United States; Department of Psychology, University of Wisconsin, Madison, 1202 W. Johnson Street, Madison, WI 53706, United States.
  • 9Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, 1500 Highland Avenue, Madison, WI 53705, United States; Department of Medical Physics, University of Wisconsin, Madison, 1111 Highland Avenue, Madison, WI 53705, United States; Department of Psychiatry, University of Wisconsin, Madison, United States.

Abstract

BACKGROUND:

The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake.

METHODS:

[(18)F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol.

RESULTS:

Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking.

CONCLUSIONS:

The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Alcohol and nicotine comorbidity; Chronic alcohol exposure; PET imaging; Rhesus monkey; α4β2 nicotinic acetylcholine receptor

PMID:
24602361
[PubMed - indexed for MEDLINE]
PMCID:
PMC3992705
Free PMC Article
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