RT Journal Article
T1 Ethanol-induced alterations in endocannabinoids and relevant neurotransmitters in the nucleus accumbens of fatty acid amide hydrolase knockout mice.
A1 Pavon, Francisco J
A1 Serrano, Antonia
A1 Stouffer, David G
A1 Polis, Ilham
A1 Roberto, Marisa
A1 Cravatt, Benjamin F
A1 Martin-Fardon, Remi
A1 Rodriguez-de-Fonseca, Fernando
A1 Parsons, Loren H
K1 Alcohol
K1 Endocannabinoid
K1 Fatty acid amide hydrolase (FAAH)
K1 Microdialysis
K1 Nucleus accumbens
AB Deletion of fatty acid amide hydrolase (FAAH), enzyme responsible for degrading endocannabinoids, increases alcohol consumption and preference. However, there is a lack of data on neurochemical events in mice exposed to alcohol in the absence of FAAH. Extracellular levels of endocannabinoids and relevant neurotransmitters were measured by in vivo microdialysis in the nucleus accumbens (NAc) of FAAH knockout (KO) and wild-type (WT) mice during an ethanol (EtOH; 2 g/kg, ip) challenge in EtOH-naive and repeated (r) EtOH-treated mice. In both genotypes, EtOH treatment caused no changes in baseline endocannabinoid levels, although FAAH KO mice displayed higher baseline N-arachidonoylethanolamine levels than WT mice. EtOH challenge caused a sustained increase in 2-arachidonoylglycerol (2-AG) levels in EtOH-naive WT mice but not in FAAH KO mice. In contrast, 2-AG levels were decreased following EtOH challenge in (r)EtOH-treated mice in both genotypes. Whereas (r)EtOH-treated mice showed higher baseline dopamine and serotonin levels than EtOH-naive mice in WT mice, these differences were attenuated in FAAH KO mice. Significant differences in baseline γ-aminobutyric acid (GABA) and glutamate levels by EtOH history were observed in WT mice but not in FAAH KO mice. Moreover, opposed effects on glutamate response were observed after EtOH challenge in EtOH-naive and (r)EtOH-treated FAAH KO mice. Finally, FAAH deletion failed to show EtOH-induced locomotion sensitivity. These data provide evidence of a potential influence of 2-AG in the neurochemical response to EtOH exposure in the NAc.
PB Wiley
YR 2019
FD 2019-10-29
LK http://hdl.handle.net/10668/13175
UL http://hdl.handle.net/10668/13175
LA en
NO Pavón FJ, Serrano A, Stouffer DG, Polis I, Roberto M, Cravatt BF, et al. Ethanol-induced alterations in endocannabinoids and relevant neurotransmitters in the nucleus accumbens of fatty acid amide hydrolase knockout mice. Addict Biol. 2019 Nov;24(6):1204-1215
NO National Institute on Alcohol Abuse and Alco-holism, Grant/Award Numbers: AA020404,AA022249, AA024146, AA017447 and ARCAA006420; Instituto de Salud Carlos III (ISCIII)and European Regional Development Funds‐European Union (ERDF‐EU), Grant/AwardNumbers: RD16/0017/0001, PI16/01953,PI16/01689, PI17/02026, CP14/00212 andCP14/00173; Plan Nacional sobre Drogas,Grant/Award Number: PND2017/043; Juntade Andalucía, Plan Andaluz de Investigación,Desarrollo e Innovación and ERDF‐EU, Grant/Award Number: PAIDI CTS‐433
DS RISalud
RD Apr 10, 2025