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Effects of Naltrexone and Acamprosate on Alcohol-Induced NGFI-A Expression in Mouse Brain
Authors:Jeanette Lindholm  Marc Guitart-Masip  Homa Hassankhali  Sara Landgren  Camille Nicoleau  Lydia Giménez-Llort  Lars Terenius  Sven Ove Ögren  Björn Johansson
Affiliation:Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Abstract:In search for the substrate of naltrexone and acamprosate action on alcohol craving, we investigated the effects of ethanol alone and combined with naltrexone or acamprosate on expression of nerve growth factor-inducible clone A (NGFI-A; zif268). In Experiments 1 and 3, alcohol (2 g/kg) alone or in combination with naltrexone (15 mg/kg) or acamprosate (300 mg/kg) was injected intraperitoneally into mice. In Experiment 2, treatment was nor-BNI (0.5 mg/kg) to investigate whether the effect of naltrexone involved blockade of κ-opioid receptors. Both ethanol and naltrexone alone induced NGFI-A in the central amygdala, but not in several other areas; these effects were additive. However, acamprosate alone or in combination with ethanol had no effect on NGFI-A mRNA, while nor-BNI induced NGFI-A mRNA in the basolateral amygdala. The central amygdala appears to be an important target of both alcohol and naltrexone. Acamprosate may not share the site of action with naltrexone despite being used for the same therapeutic purpose. Special issue article in honor of Dr.Ji-Sheng Han.
Keywords:Acamprosate  Amygdala  Ethanol  Naltrexone  NGFI-A   zif268
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