Exploring the role of central astrocytic glutamate uptake in ethanol reward in mice

Alcohol Clin Exp Res. 2014 May;38(5):1307-14. doi: 10.1111/acer.12361. Epub 2014 Mar 21.

Abstract

Background: Alcoholism is associated with specific brain abnormalities revealed through postmortem studies, including a reduction in glial cell number and dysregulated glutamatergic neurotransmission. Whether these abnormalities contribute to the etiology of alcoholism, are consequences of alcohol use, or both is still unknown.

Methods: We investigated the role of astrocytic glutamate uptake in ethanol (EtOH) binge drinking in mice, using the "drinking in the dark" (DID) paradigm by blocking the astrocytic glutamate transporter (GLT-1) with intracerebroventricular (ICV) administration of dihydrokainic acid (DHK). To determine whether astrocytic glutamate uptake regulates the conditioned rewarding effects of EtOH, we examined the effects of ICV DHK on the acquisition and expression of EtOH-induced conditioned place preference.

Results: Blocking central astrocytic glutamate uptake selectively attenuated EtOH binge drinking behavior in mice. DHK did not alter the acquisition or expression of preference for EtOH-associated cues, indicating that reduced astrocytic glutamate trafficking may decrease binge-like drinking without altering the conditioned rewarding effects of EtOH.

Conclusions: Several alternative conclusions are plausible, however, interpreting these data in the context of the human literature, these findings suggest that the reduction of glia in the alcoholic brain may not be a predisposing factor to developing alcoholism and could be a consequence of EtOH toxicity that decreases excessive EtOH intake.

Keywords: Astrocyte; Drinking in the Dark; Ethanol; Glutamate; Place Preference.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Drinking / physiopathology*
  • Amino Acid Transport System X-AG / antagonists & inhibitors
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / physiology*
  • Ethanol / pharmacology*
  • Glutamic Acid / metabolism*
  • Glutamic Acid / physiology
  • Infusions, Intraventricular
  • Kainic Acid / analogs & derivatives
  • Kainic Acid / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Reward*

Substances

  • Amino Acid Transport System X-AG
  • Ethanol
  • Glutamic Acid
  • dihydrokainic acid
  • Kainic Acid