Consequences of low or moderate prenatal ethanol exposures during gastrulation or neurulation for open field activity and emotionality in mice.
In a previous study we used a mouse model for ethanol exposure during gastrulation or neurulation to investigate the effects of modest and occasional human drinking during the 3rd or 4th week of pregnancy (Schambra et al., 2015). Pregnant C57Bl/6J mice were treated by gavage during gastrulation on gestational day (GD) 7 or neurulation on GD8 with 2 doses 4h apart of either 2.4 or 2.9g ethanol/kg body weight, resulting in peak blood ethanol concentrations (BECs) of 104 and 177mg/dl, respectively. We found that mice exposed to the low dose on either day were significantly delayed in their neonatal sensorimotor development. In the present study, we tested the same cohort of mice in an open field as juveniles on postnatal day (PD) 23-25 and as young adults on PD65-67 for prenatal ethanol effects on exploration and emotionality with measures of activity, rearing, grooming and defecation. We evaluated the effects of dose, sex, day of treatment and day of birth by multiple regression analyses. We found that, compared to the respective gavage controls, juvenile mice that had been prenatally exposed to the low BEC on either GD7 or GD8 were significantly hypoactive on the first 2 test days, reared significantly more on the last 2 test days, and groomed and defecated significantly more on all 3 test days. Only mice that had been treated on GD7 remained hypoactive as adults. Juvenile mice prenatally exposed to the moderate BEC on GD7 groomed significantly more, while those exposed on GD8 reared and defecated significantly more. Sex differences were highly significant in adult control mice, with control males less active and more emotional than females. Similar, but smaller, sex differences were also evident in adults exposed to ethanol prenatally. Persistence into later life of a deleterious effect of premature birth (i.e., birth on GD19 rather than GD20) on weight and behavior was not consistently supported by these data. Importantly, mice shown previously to be delayed in sensorimotor development as neonates, in the present study demonstrated hypoactivity and increased emotionality in open field behaviors as juveniles, and those mice exposed during gastrulation remained hypoactive as adults. Thus, we propose that the delayed motor development, hypoactivity and emotionality we observed in mice exposed to a low BEC during gastrulation or neurulation may relate to an attention deficit-activity disorder in humans, possibly the inattentive subtype, or Sluggish Cognitive Tempo (SCT). We further discuss concerns about occasional light or moderate alcohol consumption during the 3rd or 4th week of human pregnancy.
Department Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA. Electronic address: schambra@etsu.edu.
Uta B
UB
Schambra
Department Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Kevin
K
Nunley
Department Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA.
Theresa A
TA
Harrison
Department of Mathematics & Statistics, College of Arts and Sciences, East Tennessee State University, Johnson City, TN 37614, USA.
C Nicole
CN
Lewis
D000818:Animals; D003672:Defecation / Q000187:drug effects; D004644:Emotions / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D054262:Gastrulation; D006120:Grooming / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D054261:Neurulation; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*
D000431:Ethanol