Brain Development: Normal Processes and the Effects of Alcohol ...

weaning age and adulthood . Whe n expose d t o ethe r
or shock, for example, the plasm a CORT response of
the weanling shows a later peak and delayed return to
resting concentration s compared with th e patter n i n
adulthood (Goldman et al, 1973).
In summary, in the rat, the postnatal period is critical
for the developmen t and integratio n of the CN S
and peripheral nervous system mechanisms necessary
to maintain homeostasis. I n contrast , many of these
systems reach a greater degree of organization at birth
in guine a pigs , sheep, nonhuma n primates , and hu -
mans (Weaver et al., 2004).
GESTATIONAL ETHANOL
EXPOSURE AND HP A ACTIVITY
Human Studies
Compared t o the fairl y larg e literature on the effect s
of ethanol consumption on the HP A axis of adults following
acut e o r chroni c ethano l intake , onl y a few
human studie s have examined the effect s o f drinking
during pregnanc y o n th e HP A axi s o f th e develop -
ing child . I n cas e studie s b y Roo t an d colleague s
(1975), plasma cortisol concentrations are within normal
rang e i n childre n wit h FASD . B y contrast, dat a
from Jacobson and colleague s (1999 ) show that heavy 7
drinking during pregnancy and a t conception ar e associated
with higher basal and post-stress (blood draw)
cortisol concentrations i n 13-month-ol d infants. Basal
cortisol concentrations are also higher in 2-month-old
infants expose d i n uter o t o ethano l o r cigarette s
(Ramsay et al., 1996) . Animal studies strongly support
this finding that ethano l exposur e i n utero ca n hav e
major effect s o n developmen t an d functio n o f th e
offspring HP A axis. Not surprisingly , HPA activity in
the pregnan t femal e i s also altered b y ethano l consumption.
Animal Studie s
Effects of Ethanol Consumption on
HPA Activity of the Pregnant Female
Data fro m roden t model s indicat e tha t gestationa l
ethanol consumption increases adrenal weights, basal
CORT concentrations , th e COR T stres s response ,
and the CORT stress increment in the pregnant dam
(Weinberg and Bezio , 1987) . This occurs a s early as
ETHANOL EFFECTS ON ENDOCRINE AND IMMUNE FUNCTION 15 9
gestational da y (G) 11 , persists throughout gestation ,
may increase as gestation progresses, and occurs even
with low concentrations o f ethanol i n the die t (Weinberg
and Bezio , 1987 ; Weinber g and Gallo , 1982) .
Importantly, thi s activatio n appears to b e relate d t o
ethanol rather tha n t o nutritional factor s a s maternal
nutritional status has no major impact on these effect s
(Weinberg and Bezio , 1987) . The stimulator y effect s
of ethanol o n basal hormone concentration s and th e
corticoid response to stressors also can extend throug h
parturition, eve n whe n ethano l administratio n i s
discontinued prio r t o parturitio n (Weinberg , 1989) .
Thus regula r consumption o f high dose s o f ethano l
during pregnancy not only raises the set point of HPA
function i n th e pregnan t femal e b y increasin g both
basal an d stres s concentrations of CORT but als o results
in HPA hyperresponsiveness to stressors. The ad -
ditional finding that binding capacity of corticosterone
binding globuli n (CBG ) i n ethanol-consumin g fe -
males is similar to or less than that in control females,
both durin g pregnanc y an d a t parturition , indicate s
that the elevated CORT concentrations are functionally
important an d support s the conclusio n tha t pre -
natal ethanol exposur e results in both hypersécrétio n
and hyperresponsivenes s of the HP A axi s (Weinber g
and Bezio, 1987 ; Weinberg, 1989) .
The pregnan t femal e an d th e fetu s constitut e a n
interrelated functiona l unit. Hence, ethanol-induced
alterations i n HP A activit y i n th e pregnan t femal e
have implications for fetal HPA development. COR T
crosses the placenta , a t least to some extent (Eguchi,
1969), resultin g i n suppressio n o f endogenou s feta l
HPA activity. At the same time, ethanol ca n cros s the
placenta an d directl y activate the feta l HP A axis. Together
thes e influences may have permanent organi -
zational effect s o n neura l structure s tha t regulat e
HPA activit y throughout lif e (Levin e an d Mullins ,
1966). Whether th e increased plasma CORT concentration
i n pregnant female s plays a role i n mediatin g
HPA hyperresponsivenes s i n feta l ethanol-expose d
(FEE) offsprin g i s as yet unresolved . Adrenalectom y
(ADX) o f the pregnan t dam ha s n o effec t o n th e in -
creased CORT responses to restraint stress in FEE female
offsprin g (Slon e an d Redei , 2002) . Similarly ,
CORT treatment o f ADX dams does no t mimi c th e
effect o f prenatal ethanol exposure on HPA activity of
offspring (Le e and Rivier , 1992 ) On th e basis of these
data, i t appear s tha t th e increase d stres s responsive -
ness of FEE offsprin g i s not mediated primarily by increased
COR T concentration s i n pregnan t females .