In vivo and in vitro ethanol exposure in prenatal rat brain: GABA(B) receptor modulation on dopamine D(1) receptor and protein kinase A.
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(1)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 GABA(B)Rs, under 50 microM baclofen and 100 microM 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 GABA(B)Rs. Further, baclofen and phaclofen administration significantly affected PKA and GABA(B)R 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 GABA(B)R 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.
Lee
H Y
HY
Division of Life Science, College of Natural Sciences and Applied Life Science (Brain Korea 21), Gyeongsang National University, Chinju 660-701, South Korea.
Naha
N
N
Li
S P
SP
Jo
M J
MJ
Naseer
M I
MI
Naseer
M L
ML
Park
M S
MS
Park
T J
TJ
Chung
B C
BC
Kim
M O
MO
D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000196:embryology / Q000503:physiopathology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002492:Central Nervous System Depressants; D018755:GABA Agonists; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D018080:Receptors, GABA-B; D000431:Ethanol; D017868:Cyclic AMP-Dependent Protein Kinases; D001418:Baclofen