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

154 ETHANOL-AFFECTE D DEVELOPMENT
to drugs or other toxic agents, ca n permanentl y organize
o r imprint physiological and behaviora l systems
and increas e vulnerabilit y t o illnesse s o r disorder s
later i n lif e (Matthews , 2000 , 2002 ; Bakke r e t al ,
2001; Welberg and Seckl , 2001).
The presen t Chapte r focuse s o n th e advers e ef -
fects of prenatal ethanol exposur e on neuroendocrin e
and immun e function , wit h particula r emphasi s o n
the concept of fetal programming and the HP A axis, a
key playe r i n th e stres s response . Th e HP A axi s i s
highly susceptibl e t o programmin g durin g feta l an d
neonatal developmen t (Matthews , 2000 , 2002 ; Wel -
berg an d Seckl , 2001) . Earl y environmental experi -
ences, includin g exposure to ethanol, ca n reprogra m
the HP A axi s suc h tha t HP A ton e i s increase d
throughout life . Thi s chapte r present s dat a demon -
strating tha t gestationa l ethano l exposur e increase s
HPA activity in both th e pregnant female and th e off -
spring. Evidenc e suggestin g that increase d exposur e
to endogenou s glucocorticoid s ove r th e lifespa n ca n
alter behavioral and physiological responsiveness and
predispose th e organis m t o developmen t o f certai n
diseases late r i n lif e i s also described . Alteration s i n
immune function may be one of the consequence s o f
fetal HP A programming. Th e chapte r discusse s stud -
ies demonstratin g tha t ethano l i s an immunoterato -
genic agen t an d tha t programmin g o f HP A activity
may mediat e som e o f the advers e effect s o f prenatal
ethanol exposur e o n immun e competenc e i n late r
life.
THE CONCEPT O F STRESS
The ter m stress, used in the biological sense, was popularized
by Hans Selye , who proposed tha t stres s can
be understoo d withi n th e contex t o f th e "genera l
adaptation syndrome. " Thi s concep t gre w ou t o f
Selye's observation s that a wid e variet y of physically
noxious stimuli , suc h a s col d o r hea t exposure , sur -
gery, muscular exercise , bacteria, toxins, or X-irradiation,
resulted in essentially the same triad of symptoms:
(1) adrena l cortica l enlargement , (2 ) thymic involu -
tion o r atrophy, and (3 ) gastrointestinal ulcers (Selye ,
1936, 1950) .
The respons e tria d hold s despit e th e fac t tha t a
highly specific adaptive response exist s for any one o f
these agents by itself. These symptoms are considere d
a nonspecific adaptive response o f the bod y to a physical
stressor and par t of the "alar m reaction, " th e first
stage o f the genera l adaptatio n syndrome . This stag e
is characterized b y activation of the HP A system, an d
the correspondin g change s i n immune functio n an d
gastric ulcération are thought to be mediated t o som e
extent b y this HPA activation. If the stressfu l stimulu s
persists, the organism enters the second, or resistance,
phase o f th e genera l adaptatio n syndrome , durin g
which adrenocortica l activatio n i s maintained. Afte r
repeated o r constan t exposur e t o th e stresso r the or -
ganism enter s th e thir d phase , whe n th e capacit y of
the adrena l corte x t o synthesize , store , an d secret e
glucocorticoids i s exceeded (Selye , 1946) . Althoug h
not all aspects of the general adaptation syndrome are
supported b y subsequent experimenta l evidence , thi s
concept has provided a powerful context fo r stress research
fo r many years.
The concep t of nonspecificity (Sely e 1936 , 1950 )
has raise d a critica l question : throug h wha t mecha -
nisms coul d s o man y divers e agent s transmi t th e
common "message " of stress ? Sely e speculate d tha t
there mus t b e som e physiologica l "firs t mediator " o f
stress, i.e. , som e nonspecifi c chemica l o r byproduc t
of biological reaction s that produced thes e symptom s
indicative o f stres s (Mason , 1975) . Th e searc h fo r
physiological firs t mediator s wa s largel y unproduc -
tive. By the 1960s , stres s researchers became increas -
ingly awar e tha t (a ) psychologica l an d socia l factor s
had effect s simila r to and perhap s eve n mor e poten t
than thos e o f physical stressors and (b ) that th e HP A
axis wa s particularly sensitive t o thes e psychologica l
stimuli (Mason , 1968) . Thi s growin g understandin g
of th e rol e o f psychologica l variable s le d Maso n
(1975) t o sugges t tha t th e unrecognize d firs t media -
tors i n man y o f Selye' s experiment s ma y hav e bee n
the substrat e i n the central nervou s system (CNS) in -
volved in emotional arousal . That HPA activation frequently
occurred durin g novel or aversive stimulation
is not surprising because th e HP A axis is an excellen t
indicator o f arousa l (Henness y an d Levine , 1979) .
This understanding altere d th e concep t o f nonspeci -
ficity, at least in terms of the HP A response. Instea d of
viewing hormona l response s a s bein g elicite d b y a
great diversity of stimuli, they coul d b e viewed as being
elicited largel y by the emotiona l arousa l or activation
commo n t o mos t i f no t al l nove l an d aversiv e
situations.
A concept o f stress emphasizing the "emergency "
function o f the sympatheti c nervou s system an d th e
adrenal medull a an d thei r role s i n maintainin g in -
ternal homeostasi s come s fro m th e wor k of Cannon