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Excessive alcohol consumption is blocked by glial cell line-derived neurotrophic factor

The Ernest Gallo Research Center, 5858 Horton St, Ste 200, Emeryville, CA 94608, USA.
Alcohol (Fayetteville, N.Y.) (Impact Factor: 2.04). 03/2009; 43(1):35-43. DOI: 10.1016/j.alcohol.2008.12.001
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ABSTRACT We previously found that activation of the glial cell line-derived neurotrophic factor (GDNF) pathway in the ventral tegmental area (VTA) reduces moderate alcohol (ethanol) intake in a rat operant self-administration paradigm. Here, we set out to assess the effect of GDNF in the VTA on excessive voluntary consumption of ethanol. Long-Evans rats were trained to drink large quantities of a 20% ethanol solution in an intermittent-access two-bottle choice drinking paradigm. The rats were given three 24-h sessions per week, and GDNF's actions were measured when rats achieved a baseline of ethanol consumption of 5.5g/kg/24h. We found that microinjection of GDNF into the VTA 10min before the beginning of an ethanol-drinking session significantly reduced ethanol intake and preference, but did not affect total fluid intake. We further show that GDNF greatly decreased both the first bout of excessive ethanol intake at the beginning of the session, and the later consummatory activity occurring during the dark cycle. These data suggest that GDNF is a rapid and long-lasting inhibitor of "binge-like" ethanol consumption.

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Available from: Sebastien Carnicella, Aug 16, 2015
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    • "Of interest, the role of repeated cycles in ethanol exposure has also been shown in the chronic and intermittent ethanol vapor exposure that leads to a higher ethanol consumption compared to continuous ethanol vapor inhalation (O'Dell et al. 2004). In the intermittent access to 20% ethanol procedure, animals are highly motivated to consume ethanol for its pharmacological effects and exhibit 'binge-like' drinking behavior (Carnicella, Amamoto & Ron 2009). In this paradigm, NaB significantly decreased ethanol consumption when the escalation was already established. "
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    • "2.7. Intermittent access 20% alcohol two-bottlechoice drinking paradigm The intermittent access 20% alcohol two-bottle-choice drinking paradigm induces voluntary intake of high amounts of alcohol (Wise, 1973; Simms et al., 2008) and pharmacological relevant blood alcohol concentrations (Simms et al., 2008; Carnicella et al., 2009). In brief, the rats (n = 20) were given free access to one bottle of 20% alcohol and one bottle of water during three 24-h-sessions per week (Mondays, Wednesdays and Fridays), approximately 10 min after the lights went out in a reversed light/dark cycle room. "
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    • "intermittent-access to 20% alcohol 2-bottle choice drinking procedure was conducted as described previously (Carnicella et al., 2009). Briefly, rats were given 24 hr of concurrent access to one bottle of 20% alcohol (v/v) in tap water and one bottle of water. "
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