Effects of naltrexone and acamprosate on alcohol-induced NGFI-A expression in mouse brain.
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 kappa-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.
Lindholm
Jeanette
J
Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Guitart-Masip
Marc
M
Hassankhali
Homa
H
Landgren
Sara
S
Nicoleau
Camille
C
Giménez-Llort
Lydia
L
Terenius
Lars
L
Ogren
Sven Ove
SO
Johansson
Björn
B
D000077443:Acamprosate; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009271:Naltrexone / Q000494:pharmacology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D013654:Taurine; D000431:Ethanol; D009271:Naltrexone; D000077443:Acamprosate