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

FIGURE 10- 1 Schemati c representatio n of circuitry of
the stress system. The tw o major system s central to the
stress respons e ar e th e hypothalamic-pituitary-adrena l
(HPA) axis and the locus coeruleus noradrenergic sympathetic
adrenal medullary (LC-NE) system , which interact
to maintain homeostasis . Th e HP A axis consists
of a cascade o f responses. Corticotropin-releasing hor -
mone (CRH) , secrete d b y th e hypothalamus , stimu -
lates th e releas e o f adrenocorticotropi c hormon e
(ACTH) fro m th e anterio r pituitary , which i n tur n
stimulates release of the glucocorticoid hormones fro m
the adrena l cortex . Th e glucocorticoid s fee d bac k a t
multiple levels of the axi s to inhibit activity. In the LC -
NE system , norepinephrine (NE) , release d primarily
from sympatheti c nerv e terminals , an d epinephrine ,
released primaril y from th e adrena l medulla , activat e
sympathetic responses. Homeostasis is restored by activation
of the parasympathetic system. The LC-N E system
allow s the organis m t o reac t rapidly , while th e
HPA hormones act over a longer time frame. There are
intimate reciproca l interactions between th e HP A axis
and th e LC-N E system , a s well a s reciproca l neura l
connections betwee n th e tw o systems. CRH an d N E
stimulate each other, and the two systems are regulated
by similar neurotransmitters and b y mesocortical an d
mesolimbic influences . Glucocorticoid s ar e though t
to restrain both system s to prevent the consequence s
of prolonge d o r excessiv e activation . Finally , activit y
and sensitivit y of both system s are modulated by stress
and circadia n influences . AVP, arginine vasopressin;
BZD, benzodiazepine ; GABA , y-aminobutyri c acid ;
NPY, neuropeptid e Y ; POMC, proopiomelanocortin ;
ETHANOL EFFECTS ON ENDOCRINE AND IMMUNE FUNCTION 15 5
and colleague s (Canno n 1914 , 1929 ; Canno n an d
de la Paz, 1911) . Accordingly, homeostasi s i s viewed
as th e operatio n o f coordinate d physiologica l pro -
cesses that maintain the steady state of the organism.
These authors also recognize th e importanc e o f psychological
ove r physica l stimul i i n elicitin g a stres s
response.
In moder n stres s research , i t i s no w widel y ac -
cepted tha t the respons e to stress is mediated b y both
the HP A axis and th e locu s coeruleu s noradrenergi c
sympathetic adrena l medullar y system (referre d t o as
the LC-NE system) and that these system s interact to
maintain homeostasi s (Fig . 10-1) . Th e LC-N E system
i s involved i n th e "fight-or-flight " respons e an d
enables th e organis m t o reac t rapidly . Tw o majo r
players i n thi s rapi d respons e ar e norepinephrin e
(NE), secreted from sympathetic nerve terminals, and
epinephrine, release d fro m th e adrena l medulla . I n
contrast, th e HP A axis acts ove r a longer tim e fram e
and help s orchestrat e th e respons e an d adaptatio n of
the bod y to the stresso r through variou s physiological
and metabolic changes .
The ter m stress ha s prevaile d ove r decade s be -
cause i t attempt s t o addres s a basi c principl e o f na -
ture: (1) the maintenance o f balance, equilibrium , or
harmony i n th e fac e o f disturbin g stimul i an d (2 )
the counteracting , re-establishin g response s tha t re -
establish homeostasi s (Chrouso s e t al. , 1988) . Man y
definitions an d meaning s hav e been an d stil l are ascribed
t o the term stress, largely because the term has
been use d to refer t o the disturbin g stimuli, the stat e
of disturbe d equilibrium , and/o r th e result s o f th e
counteracting responses . Thi s chapte r use s th e fol -
lowing definition s (Johnso n e t al. , 1992 ; Mille r an d
O'Callaghan, 2002). Stress is a state of threatened in -
ternal balance or homeostasis. The threatenin g or disturbing
force s ar e define d a s stressors. Thes e ca n
range from rea l threats to survival (e.g., immune chal -
lenges or physical stressors) to perceived threats (e.g.,
psychological o r socia l stressors) . The counteractin g
forces activate d t o neutraliz e th e effect s o f a stressor
are adaptive responses, which ca n b e both behaviora l
and physica l o r physiological , an d serv e t o re -
establish homeostasis.
SP, substanc e P . Activatio n i s represente d b y soli d
lines, inhibitio n b y dashe d lines . (Source: Reprinte d
from Chrousos (1998) with permission fro m Ne w York
Academy of Sciences)