In vivo and in vitro ethanol exposure in prenatal rat brain: GABAB receptor modulation on dopamine D1 receptor and protein kinase ASynapse 62:534-543, 2008
We have investigated the effects of prenatal ethanol exposure on GABAB receptors (GABABRs), protein kinase A (PKA), and DA D1 receptor (DAD1R) expressions. GABAB1R and GABAB2R 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 GABABR 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 DAD1R through GABABRs, under 50
M baclofen and 100 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, DAD1R showed increasing effects upon ethanol treatment, which was modulated by GABABR'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 DAD1R activities, and may be an underlying cause of ethanol's effects.
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Request Reprint E-Mail: mokim@gsnu.ac.kr
_______________________________________________________________
We have investigated the effects of prenatal ethanol exposure on GABAB receptors (GABABRs), protein kinase A (PKA), and DA D1 receptor (DAD1R) expressions. GABAB1R and GABAB2R 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 GABABR 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 DAD1R through GABABRs, under 50
M baclofen and 100 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, DAD1R showed increasing effects upon ethanol treatment, which was modulated by GABABR'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 DAD1R activities, and may be an underlying cause of ethanol's effects.
Read Full Abstract
Request Reprint E-Mail: mokim@gsnu.ac.kr
_______________________________________________________________
