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

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

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.

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

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcohol Drinking / metabolism*
  • Animals
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / metabolism
  • Ethanol / administration & dosage
  • Ethanol / pharmacology*
  • Frontal Lobe / drug effects*
  • Frontal Lobe / metabolism
  • Functional Neuroimaging
  • Geniculate Bodies / drug effects*
  • Geniculate Bodies / metabolism
  • Macaca mulatta
  • Male
  • Positron-Emission Tomography
  • Pyridines
  • Pyrroles
  • Receptors, Nicotinic / metabolism*
  • Self Administration

Substances

  • Pyridines
  • Pyrroles
  • Receptors, Nicotinic
  • nicotinic acetylcholine receptor alpha4 subunit
  • nicotinic receptor beta2
  • nifene
  • Ethanol