Neuroscience &BiobehavioralReviews, Vol. 4, pp. 77-86. Printed in the U.S.A.
The Role of Endorphins in Stress:
Evidence and Speculations
S H I M O N A M I R , 2 Z A V I E W. B R O W N A N D Z A L M A N A M I T
Center for Research on Drug Dependence, Department o f Psychology, Concordia University
1455 de Maisonneuve Blvd. West, Montreal, Quebec, Canada
R e c e i v e d 2 N o v e m b e r 1979
AMIR, S., Z. W. BROWN AND Z. AMIT. The role of endorphins in stress: Evidence and speculations. NEUROSCI.
BIOBEHAV. REV. 4(1) 77-86, 1980.--Several lines of evidence suggest that the endogenous opioid peptides endorphins
may play a role in the defensive response of the organism to stress. The present paper summarizes these findings as well as
evidence linking endorph/ns to the anterior pituitary polypeptide hormone adrenocorticotropin (ACTH). Evidence is
presented that endorphins may function as trophic hormones in peripheral target organs such as the adrenal medulla and the
pancreas. As such they may be part of the physiological mechanisms that mediate adrenaline and glucagon release in
response to stress. Endorphins (enkephalins) are also suggested to play a role in the control of the pituitary gland during
stress. In such capacity they may act as hormone-releasing or inhibiting factors. Finally, endorphins appear to play a role in
the behavioral concomitants of stress. In such capacity eodorphins are suggested to function as modulators of neural
systems that mediate the elaboration and expression of the reactive/affective components of stress. Speculations on the
mode of interaction between eodorphins and ACTH in the global response to stress are discussed.
Stress
Endorphins
Analgesia
Affect
Enkephalins
Pituitary gland
ACTH
Opiate receptor
T H E R E is growing awareness that opioid peptides
endorphins represent a new class of neurotransmitters and
modulators, common to the central and somatic divisions of
the nervous and endocrine systems, and that they may serve
to regulate neural and endocrine functions that play a role in
the elaboration of adaptive behavior [15, 25, 55, 68, 79, 119,
128, 130, 169, 170, 185, 228]. It is becoming increasingly
evident, however, that these peptide systems may not function tonically but that they influence physiological and behavioral processes in a rather selective manner, only under
specific environmental conditions or endogenous factors
(e.g. [1, 36, 42, 48, 49, 58, 62, 86, 89, 91, 95, 100, 109, 113,
127, 137, 142, 146, 157, 194, 230, 240]). Evidence accumulated recently indicate that endorphins are released from
the pituitary gland in response to stress concomitantly
with the hormone adrenocorticotropin (ACTH), and that
structural relationships exist between the two classes of
polypeptides [94,156]. Furthermore, there is evidence that
stress may activate endorphin systems in the brain as well
[3,190]. These findings suggest that endorphins may play a
role in the global defensive response to stress, and that their
physiological functioning may be related in some fashion to
the functions to the hormone ACTH. ACTH is known
primarily for its role in the release of steroid hormones from
the adrenal cortex and for its direct metabolic effects, which
enable the organism to better adjust to extreme changes in
circumstances [63,204]. Additionally, ACTH possesses various central nervous system effects, which are independent
Adrenal medulla functioning
Pain
of its somatotropic functions, and it appears to influence
motivation and arousal and other central processes that play
a role in adaptive behavior [33, 52, 56, 79, 130, 168].
In the present article we review evidence on the involvement of endorphins in the global response of the organism to
stress. We describe findings that endorphins and ACTH are
part of the same neuroendocrine system but that they may
normally produce differential physiologic and behavioral effects. Furthermore, we propose several hypotheses concerning a functional link between the endorphins and physiological mechanisms that play a role in stress. Finally we examine findings on the role of endorphins in the behavioral response to stress and suggest that they may mediate the elaboration and expression of the reactive/affective components
of stress.
BIOCHEMICALEVIDENCEFOR THE INVOLVEMENTOF
ENDORPHININ STRESS
The opioid peptides betaoendorphin and enkephalin occur
in cells and processes of the central and autonomic nervous
system and in the central and somatic divisions of the
endocrine system. Beta*endorphin is found in the pituitary
gland [14, 85, 106, 152, 195, 219], particularly in the pars
intermedia and adenohypophysis [24,188]. Additionally, it
occurs within the brain, with a single cell group in the
hypothalamus and large axons innervating iimbic and mid=
brain structures [37,191]. Enkephalin systems, with multiple
1Presented at a Workshop on Stress and Environmentally Induced Analgesia, Eastern Psychological Association annual meeting, Philadelphia, PA, April 1979.
~Present address: Isotope Department, Center for Neuroscience and Behavioural Research, The Weizmann Institute of Science, Rehovot,
Israel.
77
78
cell groups and relatively short axons occur within the brain
and spinal cord [23, 24, 59, 235], the gastrointestinal tract
[4,182], the pancreas [93], in sympathetic ganglia [53, 200202] and in many gland cells as well as in nerve fibers in the
adrenal medulla [147, 154, 201, 202]. Beta-endorphin and
enkephalin are fragments of the hormone beta-lipotropin
(endorphin: beta-lipotropin 61-91; enkephalin: betalipotropin 61-65) [45,144]. This pituitary polypeptide hormone [ 140,148] is contained within a 31,000-dalton glycoprotein molecule known as pro-opiocortin, which also contained
within its sequence the hormone ACTH [156, 186, 193].
Endorphins and ACTH are present within the same secretory granules in pituitary corticotrophic cells [ 178,238] and
there is immunocytochemical evidence that they also coexist
within the brain [37, 130, 131,151,235]. Furthermore, there
is evidence that the same environmental and endogenous
stimuli trigger the mobilization of endorphins and ACTH
from the pituitary for physiological functioning and that the
same biochemical processes are regulating this effect. Stressors known to activate the pituitary-adrenal axis (e.g. limb
fracture, foot shock, heat stress, insulin-induced hypoglycemia, ingestion of hypenonic saline, immobilization) have
been reported to decrease anterior pituitary endorphin content and to trigger a parallel increase in plasma endorphin
and ACTH levels [13, 22, 94, 132, 192, 198, 241]. A rise in
plasma endorphin and ACTH levels has also been observed
following adrenaleetomy, metyrapone or morphine administration, electroconvulsive treatment and in various pathological conditions related to pituitary hyperfunctioning [2, 61,
43, 66, 70, 77, 94, 105, 132, 231,241]. Both stress-induced
and morphine-induced release of endorphins and ACTH
were found to be blocked by the administration of the synthetic glucocorticoid dexarnethasone and by hypophysectomy [70,94]. In in vitro preparations, endorphins and ACTH
were found to be released from pituitary cells in response to
purified hypothalamic corticotropin releasing factor,
hypothalamic extract and lysine vasopressin [94, 183,224].
This effect was found to be blocked by dexamethasone and
by the administration of dopamine and its agonist apomorphine [223,224]. Alterations in brain levels of endorphins
have also been reported following exposure to stress. Foot
shock or heat stress have been shown to cause an increase
[3, 155, 240] or a decrease [190,192] in regional or whole
brain enkephalin content. However, failure to induce any
change in brain enkephalin content after such treatment has
also been reported [67]. Similarly, immobilization stress has
been reported not to produce any changes in hypothalamic
immunoreactive ACTH concentrations [129]. Repeated exposure of immature rats to heat stress resulted in an increase
in endogenous opioid content and in opiate receptor binding
capacity in brain [221]. Finally, psychological stress (conditioned fear) has been reported to result in an increase in
opiate receptor occupancy in brain, suggesting a possible
rise in peptide activity [39,40]. Social isolation, another form
of psychological stress resulted in an increase in the number
of opiate receptor binding sites in brain [34].
Taken together, the above findings suggest that activation
of endorphin systems may be an integral part of the global
defensive response of the organism to stress. Additionally,
the findings outlined suggest that endorphins and ACTH,
which appear to coexist in two distinct neuroendocrine systems (i.e. pituitary and brain), may function in a coordinated
manner to mediate both the physiological and the behavioral
consequences of stress.
AMIR. BROWN AND AMIq
ENDOCRINE FUNCTIONS FOR ENDORPHIN DURING STRESS
The fact that endorphin is released from the pituitary to
the circulation in response to stress suggests that it may
function as atrophic hormone at peripheral target organs,
and that like ACTH, it may modulate the activity of
endocrine systems that play a role in stress. Several studies
suggest that endorphins may play a role in the control of
catecholamine release from the adrenal medulla. Stressinduced adrenaline release from the adrenal medulla is controlled predominantly by trans-synaptic input from the
splanchnic nerve [38, 139, 176, 220]. Morphine has been
shown to influence adrenaline synthesis and storage and to
stimulate adrenaline release from the adrenal medulla directly, even after chronic and complete denervation of this
gland [10, 11,248]. Furthermore, a population of high affinity
opiate binding sites with sensitivity to sodium ions similar to
that of brain opiate receptors has been described in bovine
adrenal medulla [41]. It is conceivable that circulating
endorphins could exert exclusive morphine-like adrenaline
releasing effects via opiate receptor systems in the adrenal
medulla and that this physiological mechanism may function
in parallel to the sympatho-adrenal axis that normally control
adrenaline release. Indeed, a hypothalamo-anterior pituitary
system that modify adrenaline release from the adrenal
medulla has been described [12,138] and endorphin has been
shown to act as a trophic hormone in kidney tissue [96].
Furthermore, the presence of enkephalins in sympathetic
ganglia [53,200-202] and in cells and nerve terminals in the
adrenal medulla [147, 154, 199, 201,202,211] suggest a role
for opioid peptides in the neural control of the adrenal
medulla. Enkephalins could interact with adrenaline-release
mechanisms after they have been secreted from the splanchnic nerve in response to stress along with other transmitter
substances (i.e. acetylcholine) that play a role in the control
of adrenaline release from the adrenal medulla. Alternatively, enkephalin could be released from the adrenal
medulla and act on "opiate-autoreceptors" on the gland ceil,
to regulate adrenaline secretion in response to stress. Finally, enkephalins could be released from the adrenal
medulla into the circulation concomitantly with adrenaline
and exert hormone-like effects at other target organs. It
should be noted that despite the rapid enzymatic degradation
of enkephalin and the reported lack of analgesic effects following intravenous administration of the peptide [98], peripherally secreted enkephalins could still play some, as yet
unidentified physiological or behavioral role in stress. This
possibility is backed by the findings that systemic administration of enkephalins to experimental animals may result in
behavioral change [119].
Endorphins may also play a role in the control of the
hypothalamo-pituitary-adrenal cortex axis. Endorphins and
opiates have been reported to stimulate in vitro corticosterone synthesis [74,206]. Since some opiate receptor binding sites occur in the adrenal cortex [41 ] it is conceivable that
endorphin, like ACTH, could exert some corticotropic effects in animals, when released into the circulation in response to stress. Alternatively, endorphin or enkephalin
could play a role in modulating stress-induced secretion of
adrenal steroids indirectly, by stimulating or reducing a
restraint on ACTH release from the pituitary gland. The release of ACTH in response to stress is triggered by the action
of corticotropin releasing factor (CRF) on the pituitary gland
[197,229]. CRF is located in neurosecretory cells in the su-
ROLE OF ENDORPHINS IN STRESS
praoptic and periventricular nuclei of the hypothalamus, where
high content of opiate receptors and of enkephalin and
endorphin immunoreactive material has been reported [37,
59, 136] and where stress-induced changes in enkephalin
levels have been observed [190,192]. The opiate antagonists
naloxone and naitrexone have been shown to block stressinduced corticosterone release in mice [75, 76, 78] while
endorphin has been reported to induce ACTH secretion from
the pituitary in rats [225]. Taken together, these data suggest
that hypothalamic opioids may play a role as corticotropin
releasing agents or that they interact with other factors (i.e.
CRF) that play a more direct mediational role in the release
of ACTH in response to stress. Interestingly, evidence accumulated in recent years strongly supports the notion that
multiple releasers rather than a unique neurohormone is
mediating the secretion of ACTH from the pituitary during
stress [197].
Opiate receptors occur in the pituitary gland, particularly
in the posterior (neural) lobe, and in the pancreas [108,207].
Furthermore, enkephalin containing neurons project from
the hypothalamus to the neural lobe [189], and enkephalinlike immunoreactivity has been found in pancreatic glucagon
cells [93]. These findings suggest a role for opioid peptides in
the control of hormones such as vasopressin, glucagon and
insulin which play a role in the global response to stress [107,
108, 116, 158,239]. Finally, endorphin and enkephalin have
been reported to play a role in the release of the anterior
pituitary hormones prolactin and growth hormone, which
also play a role in the response to stress [35, 58, 84, 88, 149,
161, 205, 226]. The findings outlined above suggest that
endorphins may play a role in the control of hormone secretion in both the central (i.e. pituitary hormones) and peripheral (i.e. adrenal and pancreas hormones) divisions of the
endocrine system. In addition they suggest a rink between
enkephalin and components of the central and autonomic
nervous system that trigger hormone release from these
endocrine systems in response to stress. Thus the findings
suggest that endorphin and enkephalin may be part of the
diffuse neuroendocrine system that may account for the
coordinated secretion of hormone substances during stress.
This idea fits well with the findings that endogenous opioids
and ACTH are mobilized simultaneously in response to
stress and it supports the notion that the two classes of peptides exert parallel trophic effects as pan of the adaptive
response to stress.
BEHAVIORALROLE FOR ENDORPHINDURINGSTRESS
The formation and execution of adaptive behavior depends to a large extent on a well coordinated interplay between neural systems that mediate sensory, motivational and
affective processes within the brain. Endorphins possess
central nervous system effects [68, 169, 171] and there is
evidence that they may play a role in the elaboration and
expression of the emotional response to stress.
Acute exposure to stressors such as electric shock, cold
water swim, restraint, insulin-induced hypoglycemia, as well
as psychological stress has been reported to modify pain
responsiveness in a large number of laboratory studies [ 125].
Stress-induced analgesia was subsequently found to depend
on the functional integrity of the pituitary gland [6, 27, 28,
102], to correlate with changes in endorphin activity [3,155]
and opiate receptor occupancy in the brain [39,40], and to be
blocked, in pan, by the opiate antagonist naloxone [3, 9, 29,
30, 42]. Hypnotic analgesia in conditions of stress was also
partially reversed by naioxone [71], but no effect of naloxone
79
~ : ~ o b s e r v e d in other ~ases of hypnotic analgesia [87,159].
The changes in pain responsiveness induced by stress resembled the analgesia induced by morphine [42] as well as
that induced by exogenously administered endorphins [222],
suggesting an opiate like role for endogenous endorphin/enkephalin systems in such effect [26,209]. Evidence from human studies suggest that a well defined separation exists between the peripheral or internal sensation of
pain and the central elaboration of that sensation (i.e. the
emotional component of pain) [18,163]. Since morphine has
been shown to exert its analgesic effects primarily by modifying the emotional component of pain [111,167] it is conceivable that stress-induced analgesia, which presumably
acts at least in part via endorphin release, may exert comparable selective effects. When placed on a hot metal plate
(51°C) within a Plexiglas enclosure rats typically exhibit two
distinct behavioral responses: a paw withdrawal accompanied by vigorous licking, and jumping that ultimately leads
to escape. Analysis of the temporal relationships between
the two response latencies suggest that the paw lick response
(short latency) may represent the sensory/perceptual components of pain while the escape behavior (long latency) may
represent the reactive/affective components of pain [9,69].
Using this paradigm it was reported that immobilization
stress, which induces the release of endorphins from the
pituitary gland [13, 57, 124], had a selective effect on escape
but it did not influence paw lick behavior [6,9]. In these
studies naloxone or hypophysectomy blocked the effect of
immobilization stress on escape but they did not influence
paw lick behavior. Elsewhere, naloxone was reported to
exert selective effects on jumping from a hot plate in mice,
suggesting that hot piate-stress may be sufficient to activate
endorphin systems so that previous exposure to stress may
not be necessary to demonstrate a selective involvement of
endorphins in the affective component of pain [6, 27, 28,
102]. Finally, chronic administration of the opiate antagonist
naltrexone resulted in enhanced sensitivity to foot shockinduced attenuation of escape from a hot plate in rats [5].
Chronic opiate receptor blockade was found previously to
increase the number of opiate receptor binding sites in the brain
as well as to result in supersensitivity to the analgesic effect
of morphine [141,212]. Interestingly, acute stress has been
shown to potentiate the hyperalgesic effect of naloxone [118]
as well as it's ability to antagonize morphine analgesia
[99,245] while hypophysectomy has been reported to block
the hyperalgesic effect of naloxone [90]. Naloxone was
found to induce contractions in ileum preparations taken
from stressed guinea pigs, but it failed to do so in ileum
preparations taken from non stres~d animals [32].
Unlike acute stress, which typically reduces pain responsiveness, prolonged exposure to stress (anxiety) could lead
to enhanced reactivity to pain [16, 17, 184]. Such effect may
be linked to a chronic reduction in the functional availability
of endorphin [203], or to a change in endorphin/ACTH ratio.
Stress-induced analgesia adapts upon repeated exposure to
the stressor [9,31], and such treatment may also lead to
hyperresponsiveness to pain and to a decreased endorphin
activity in brain [155]. Furthermore, ACTH administration
to normal or hypophysectomized-stressed rats enhanced escape from a hot plate [6]. Additionally, such treatment partially reversed the analgesic effect of cold water swim [46].
Finally, chronic elevated plasma levels of ACTH, induced
by adrenalectomy was associated with increased sensitivity
to pain in rats [102].
80
Other studies also provide evidence that endorphin systems
may play a role in modifying emotional tone during stress.
Thus, endorphins or enkephalins has been suggested to be
released in response to a stimulus that signalled shock [39,40]
while naloxone was found to block animal's preference for a
signalled versus unsignalled shock [64]. Naloxone has also
been shown to enhance shock induced freezing in rats [65] although failure of naloxone to influence the fear-induced immobility reflex in rabbits [73] or the fear induced startle response in rats [50] has also been observed. Exposure of animals to a novel environment is a stressful event and the
amount of exploration and activity under such circumstances
could be used as a measure of emotional tone. A direct correlation was demonstrated between exploratory behavior in
mice and enkephalin induced behavioral activation in these
animals [123]. Furthermore, naloxone or naltrexone were
found to depress exploratory behavior and entry into a novel
environment in mice and rats [92, 121,123]. Finally, chronic
administration of naloxone prevented the increase in activity
seen in rats upon repeated exposure to the testing environment [8]. Some stressful situations with an apparent emotional component may lead to changes in body temperature
(emotional hyperthermia). Such changes are linked to an increase in plasma endorphin-like immunoreactivity and they
are found to be blocked by the opiate antagonist naloxone
[22]. Interestingly, endorphins have been suggested to play a
role in behavioral adaptation to heat stress [104], while noise
stress has been shown to mask the hypothermic effect of
naloxone in rats [210]. Non-traumatic noice-light stress has
also been shown to increase grooming behavior in a novel
environment [122]. This effect was found to be blocked by
naltrexone, suggesting the involvement of an endogenous
opioid system in the expression of stress induced grooming
[82,122]. Finally, endorphins have been reported to reduce
distress vocalization in socially isolated chicks [175] while
naloxone was found to increass such behavior in guinea pigs
[101]. These studies suggested a role for endogenous opioids
in mediating the affective component of social stress
[34,174]. In humans, naloxone and naltrexone were found to
exert negative effects on mood [162,214].
The evidence summarized in this section suggest that the
elaboration and manifestation of behavior under conditions
of stress may be linked to the function of endogenous opioid
systems. More specifically, they suggest that endorphin may
play a rather selective role in the elaboration of emotion
during stress. The endorphin-induced changes in emotional
tone do not depend on the presence of any particular stressor. Indeed, endorphins are mobilized from the pituitary and
in the brain in response to a large number of unrelated stressors including electric shock, restraint, leg fracture, insulininduced hypoglycemia and more [13, 22, 94, 132, 192]. Furthermore, such changes may possess different behavioral
consequences. Changes in emotional-tone in response to
stress probably possess an adaptive value since they may
enable the organism to better adjust to those stressful circumstances that induced endorphin release. Such effect
would be of particular importance in the case of stressors
that involve physical injury (i.e. acute analgesia). Interestingly, the response to some forms of pain may not depend
on activation of endogenous opioid systems. While several
experiments have demonstrated lower pain resistance following naloxone administration, thus implicating endorlahins
in the normal response to pain [36, 43, 69, 109, 127, 146],
others have failed to demonstrate such effect [86, 89, 100,
1711.
AMIR, BROWN AND AMIT
Changes in endorphin activity may also lead to maladaptive consequences. For example, if endorphin release persists in the presence of a stressor, a condition which may
result from a defect in feed back control, the development
and execution of goal directed behavior (i.¢. fight, escape)
may be disrupted. Indeed, changes in affective-tone are
common characteristics of certain stress related pathological
conditions in humans (i.e. schizophrenia, depression), and it
may be linked to an abnormal activation of endorphin systems in response to stress [228]. Reports of high plasma and
CSF endorphin levels [54, 150, 214,216,233] and of reduced
sensitivity to pain [47,97] in humans suffering from affective
illness, and of the beneficial effect of naloxone in such conditions [62, 95, 145, 214, 234] give support to such idea.
However, the existence of contradictory evidence narrows
the generality of such effect [1, 49, 61, 113, 137, 187, 230].
A coordinated role for pituitary endorphin and ACTH in
the behavioral response to stress is suggested from the findings that they are released from anterior pituitary corticotrophs
in parallel in response to stress, and that the same regulatory
mechanisms are mediating the release of these peptides I94].
Pituitary endorphin and ACTH represent a distinct system
that is separated from brain endorphin and ACTH [44. 126,
129, 133, 191, 200]. It is conceivable however that small
amounts of these peptides may enter the brain via the vascular system or through the CSF after being mobilized from the
pituitary during stress [19, 20, 119, 130, 167, 172, 180, 227].
In addition, endorphin (enkephalin) may be mobilized in response to stress within the brain [155]. Endorphin and
ACTH could exert opposing effects via the same receptor
mechanisms and function as regulators of neural systems
that mediate adaptive behavior during stress. ACTH, like
endorphins, possess affinity for opiate receptors in vitro [81,
215,217,218, 242, 249]. Furthermore, ACTH was found to
counteract morphine analgesia [81, 83,242,244] as well as to
antagonize morphine-induced behavioral activation in mice
[120]. Moreover, ACTH was found to antagonize the
morphine-induced reduction in spinal reflex activity in the
cat and the depressant action of morphine on monosynaptic
activity of frog isolated spinal cord in vitro [135,249]. Finally, ACTH fragments were found to mimic the inhibitory
effect of morphine on the electrically evoked contraction of
the mouse vas deferens [181]. This effect as well as the effect
of ACTH on grooming behavior and reproductive function
was found to be blocked by naloxone and naltrexone [80, 82,
115, 181, 247] although a synergistic effect of naloxone on
ACTH [21] or no interaction between ACTH and naltrexone
has also been observed I51]. Finally, naloxone was found to
block ACTH intravenous self-administration in rats [117].
The above findings provide evidence for the existence of a
common site of action for endorphins and ACTH [7, 134,
232, 242]. They also suggest that ACTH may function in the
capacity of an endogenous antagonist for opiate receptor
systems in the brain [134,217,218,242]. Opposing effects of
endorphins and ACTH on neural excitability [165, 170, 196,
243,246] and neurotransmitter functioning in the brain [114,
153, 166, 213] have been demonstrated.
Additionally, endorphins and ACTH may function via
separate neural systems in the brain [110]. Endorphin or
enkephalin may modulate the function of limbic mechanisms
that play a role in the elaboration of emotion. The occurrence of dense population of opiate receptors [136, 143, 179]
and of opioid neurons in limbic structures [103, 208, 237],
and their interaction with central catechotamine neurons [72]
is in line with such idea. Furthermore, the occurrence of
ROLE OF ENDORPHINS IN STRESS
81
ACTH containing neurons in the hypothaiamus, thalamus,
midbrain, amygdaia and reticular formation [173, 177, 236]
suggest the presence there of ACTH receptor systems, and it
is in line with the proposed role of ACTH of central or pituitary origin in the central mediation of motivation and arousal
during stress [33,160].
The research on endorphins outlined above suggests that
these opiate-like peptides may play a role in the global response of the organism to stress. Endorphins appear to be
part of a diffuse neuroendocrine system that also contains
the hormone ACTH. Endorphins and ACTH appear to function in parallel in peripheral target organs and in the brain. In
particular, endorphins may function as trophic hormones, to
stimulate adrenaline release, or as releasing or inhibiting factors in the pituitary gland. In the brain endorphins may function to modulate neural systems that play a role in the elaboration and expression of the emotional components of behavior during stress.
The proposed behavioral role of endorphins in the media-
tion of emotion during stress is analogous to the observed
analgesic effects of exogenously administered opiates. As
discussed, opiates appear to exert selective effects on the
affective component of pain, leaving the sensory component
relatively infact. Similarly, the endogenous opiate system
may serve to modulate the affective reaction to stressful
stimuli while ACTH may be involved in the perception of
that stimuli and in preparatory functions that lead to the
response. In view of the fact that endorphins and ACTH are
released from the pituitary simultaneously in response to
stress, a coordinated action of endorphin and ACTH would
allow for the production of adaptive behavior.
ACKNOWLEDGEMENTS
We would like to thank Miss King-Yee Man for careful typing of
the manuscript. Dr. Shimon Amir was supported by the Medical
Research Council of Canada. Dr. Zavie Brown was supported by the
National Research Council of Canada.
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