In vivo and in vitro ethanol exposure in prenatal rat brain: GABA(B) receptor modulation on dopamine D-1 receptor and protein kinase A

초록

We have investigated the effects of prenatal ethanol exposure on GABA(B) receptors (GABA(B)Rs), protein kinase A (PKA), and DA D-1 receptor (DAD,R) expressions. GABA(B1)R and GABA(B2)R showed different age-dependent expressions in in vivo fetal rat forebrain from gestational days (GD) 15.5 to 21.5 upon 10% ethanol treatment to mother, with and without baclofen at a dose of 10 mg/kg body weight/day. The protein level changes could not be attributed to changes in the level of transcription since GABA(B)R mRNA presented different expression patterns upon in vivo ethanol treatment. Using in vitro cultivated cortical neurons from GD 17.5 fetuses, we also explored the modulatory effects of ethanol on PKA and DAD(1)R through GABABRs, under 50 mu M baclofen and 100 mu M phaclofen administrations, with or without 100 mM of ethanol treatment in the culture media. The results showed that 20 min ethanol treatment without baclofen or phaclofen had increasing effects on both the GABABRs. Further, baclofen and phaclofen administration significantly affected PKA and GABABR levels upon 20 min and 1 h ethanol treatment. In contrast, DAD(1)R showed increasing effects upon ethanol treatment, which was modulated by GABA(B)R's agonist baclofen and antagonist phaclofen. Therefore the present study suggested that the GABABR activity could modulate ethanol's cellular effects, which possibly including PKA and DAD(1)R activities, and may be an underlying cause of ethanol's effects.

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