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Alcohol and Alcoholism Advance Access originally published online on February 16, 2006
Alcohol and Alcoholism 2006 41(4):379-385; doi:10.1093/alcalc/agl006
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© The Author 2006. Published by Oxford University Press on behalf of the Medical Council on Alcohol. All rights reserved

WITHDRAWAL FROM FREE-CHOICE ETHANOL CONSUMPTION RESULTS IN INCREASED PACKING DENSITY OF GLUTAMINE SYNTHETASE-IMMUNOREACTIVE ASTROCYTES IN THE PRELIMBIC CORTEX OF ALCOHOL-PREFERRING RATS

JOSÉ JAVIER MIGUEL-HIDALGO

Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS 39216, USA

* Author to whom correspondence should be addressed at: Tel: +1 (601) 984-5791; Fax: +1 (601) 984-5899; E-mail: jmiguel-hidalgo{at}psychiatry.umsmed.edu

(Received 2 September 2005; first review notified 5 December 2005; in revised form 29 December 2005; accepted 16 January 2006)

Excess activation of glutamatergic neurotransmission in the cerebral cortex following ethanol withdrawal is considered to contribute to significant behavioural disturbances, and to alcohol craving. Astrocytes may play a role in these manifestations because astrocytes are essential in the regulation of released glutamate and its conversion to glutamine through the enzyme glutamine synthetase (GS). However, it is unclear if withdrawal from free-choice ethanol drinking causes changes in the numbers of astrocytes expressing GS or the cytoskeletal protein of astrocytes glial fibrillary acidic protein (GFAP). Alcohol-preferring (P) rats exposed to free-choice ethanol drinking were either maintained without forced interruption of ethanol drinking, subjected to a 3-day withdrawal period at the end of 2 months, or subjected to three 3-day withdrawal periods along 6 months. At 2 months, P rats were also compared with alcohol-naïve alcohol non-preferring rats (NP) rats. Packing density of GS and GFAP-immunoreactive (IR) astrocytes was measured in sections from the prelimbic cortex (PLC) using the optical disector probe. An alcohol deprivation effect was observed in P rats with withdrawals during a 6-month ethanol drinking period. Ethanol withdrawal significantly increased the packing density of GS- and GFAP-IR astrocytes in the PLC of P rats as compared with P rats with continuous access to ethanol. In addition, there was a positive correlation between the pre-withdrawal ethanol consumption and the packing density of GS-IR astrocytes. The present results suggest the involvement of astrocytes in the regulation of the glutamatergic activation associated with withdrawal from free-choice ethanol consumption and point to differential adaptations of GS and GFAP to prolonged alcohol drinking in the PLC of P rats.


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J Miguel-Hidalgo, Y Shoyama, and V Wanzo
Infusion of gliotoxins or a gap junction blocker in the prelimbic cortex increases alcohol preference in Wistar rats
J Psychopharmacol, July 1, 2009; 23(5): 550 - 557.
[Abstract] [PDF]


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