Brriin Rrsrcrrd~ Bdk~in. Vol. 17, pp. .51-S& 1986. A&ho International Inc. Printed in the U.S.

A 0361-9230186
$3.00 + .OO

Monosodium Glutamate Neurotoxicity:

A Sex-Specific Impairment of
Blood Pressure but not Vasopressin
in Developing Rats
RICHARD W. CLOUGH,* PAUL F. ARAVICH* AND CELIA D. SLADEK*t

Received 23 April 1986

CLGUGH, R. W., P. F. ARAVICH AND C. D. SLADEK. M~triosodi~rtn &ttrmczlc nc~ltroloxic~it~:A .w.~-.~pul,c~?jkiwzpuir-

tncnt c?f /~lrtttd pressrtrc~ hut twt ~,~i.s~~p~~.s.sit~ mts, BRAIN RES BULL 17f 1) 5 l-58, l9~.-Neonatal
iti ~l,~~~~~~pj~?~
administration of monosodium glutamate (MSG) results in severe adenohypophyseal endocrine malfunction as a result of
hypothalamic neurotoxic lesioning. The present study examined the effects of administration of MSG on the neumhypo-
physeal vasopressinergic (AVP) system and systolic blood pressure (SBP) in adulthood. Monosodium glutamate or hyper-
tonic sodium chloride was administered to male and female rat pups on days 1, 3, 5, 7 and 9 after birth. MSG treatment
produced several features characteristic of the MSG-toxicity syndrome. including obesity, anterior pituitary dysgenesis
and hypogonadism. However, MSG did not alter neurohypophyseal AVP profiles: AVP content of the posterior pituitary
and microdissected regions of the hypothalamus and brainstem were similar in MSG-treated and control rats. Furthermore,
MSG treatment did not alter water intake, serum AVP ConcenIration, or the ability to reduce urine output in response to
water deprivation. Thus, despite insult to adenohypophyseal function by neonatai administration of MSG, the neurohypo-
physeal AVP system remained functionally intact. In contrast, neonatal treatment with MSG altered SBP in a sex dependent
manner. Female MSG-treated rats, unlike male MSG-treated rats, exhibited consistent systolic hypotension when com-
pared with the NaCl-treated or non-treated control rats at 6. 9 and 12 weeks of age. Despite this chronic hypotension in
MSG-treated female rats. heart rate was not altered and serum AVP was not elevated. These observations suggest a
resetting of the baroreflex. attributable to neonatal administration of MSG.

Monosodium glutamate Blood pressure Vasopressin Water balance Dorsal vagal complex
Paraventricular hypothalamic nuclei Supraoptic hypothalamic nuclei Median eminence
Obesity Sex differences Rats

NEONATAL administration of monosodium glutamate of hypothalamo-adenohypophyseal endocrine function [ 19,

(MSG) produces neuronal degeneration in the hypothalamic 29, 401.
arcuate region and several other brain areas including the Associated with hypothalamic-adenohypophyseal dys-
circumventricular organs (CVO) and the inner layers of the function, MSG-treated animals exhibit a variety of sex-
retina [I& 24, 26, 32, 341. The extent of these lesions is related abnormalities including gonadal atrophy [29,40], re-
dependent upon the dosage of MSG and the age of the animal duced estrogen uptake into specific brain areas [39], di-
at exposure (days I-10 being regarded as the most critical in minished sexual behavior 1401, altered responsiveness of pi-
the rat [X,45]). Subsequent to the acute neurotoxic effects of tuitary gonadotrophs to exogenous luteinizing hormone-
MSG on the developing central nervous system (CNS), a releasing hormone [ 121 and impaired reproductive capacity
number of pathophysiological events occur. Among these in both male and female rats [35]. In addition, several of the
are skeletal stunting with pronounced obesity [8, 31, 451, effects of neonatal MSG appear to be gender related. For
hyperinsulinemia [IS], reduction in hypothalamic adreno- example, male and female rats differ with respect to the ef-
corticotrophic hormone (ACTH) and beta endorphin content fect of MSG on 2-deoxy-D-glucose-induced feeding [S], ac-
1221. diminished ~atecholamine histofluorescence in the tivity in a novel environment (291. and specific aspects of
hypothalamus [20], hypothermia [5], and severe impairment morphine-induced analgesia [4]. Furthermore, MSG-treated

Requests for reprints should be addressed to Celia D. Sladek, Department of Neurobiology and Anatomy, University of Rochester Medical
Center, Rochester. NY 14642.

51
5,
male mice exhibit greater thermoregulatory deficits than
female mice [ 141. Therefore. there appears to be a differen-
tial sensitivity to MSG in males and females.
Due to these diverse abnormalities, many of which repre-
sent hypothalamic regulatory functions, we hypothesized
that neonatal MSG treatment might alter hypothalamic regu-
lation of fluid and electrolyte balance and blood pressure.
Studies on the effects of MSG on these hypothalamic func-
tions are limited and contradictory. Total hypothalamic AVP
content was reported unchanged [21] and circulating AVP
levels were reported to be either unchanged [21] or elevated
[46] following neonatal MSG treatment. Neonatal MSG also
was reported to cause deficits in the AVP response to certain
stimuli [25]. Additionally, MSG treatment results in de-
creased blood pressure of both spontaneously hypertensive
(SHR) and W~star-Kyoto (WKY) rats [46). The present study
was designed to evaluate in more detail the effects of
neonatal administration of MSG on blood pressure, AVP
profiles, and the regulation of fluid and electrolyte balance.
Under basal conditions. fluid intake was measured and the
AVP system was evaluated via regional analysis of AVP
content of several brain areas. Function of the AVP system
was assessed indirectly by evaluating the urinary response to
water deprivation. Systolic blood pressures and heart rates
were monitored from 6 to 12 weeks of age. Finally. to de-
termine if a sex-dependent sensitivity to MSG exists with
regard to these parameters, both male and female rats were
examined.
METHOD
Pregnant Sprague-Dawley rats (Charles River Labora-
tories, Wilmington, MA) were housed in Plexiglas containers
in a vivarium with automatic temperature controls (24-26
degrees C) and lighting schedules (12-12). The day after birth
(day l), pups were assigned to non-treated control groups,
groups that received hypertonic sodium chloride (NaCl, 1.38
mg/g body weight, SC, to achieve equimolar sodium content
to that in MSG [21]) or MSG-treated groups (monosodium
L-glutamate, 4 mg/g body weight, SC, Sigma Chemical, St.
Louis, MO). Four control, nine NaCl and eight MSG female
rats completed the experiment. Among the male groups, five
control, nine NaCI and seven MSG rats finished all testing.
Monosodium glutamate or saline was administered to pups
on days 1, 3, 5, 7 and 9 after birth according to previous
descriptions [12]. Rats were weighed at each injection and
weaned at 21 days of age. After weaning, rats were housed in
groups of 3 in Plexiglas containers throughout the study.
Systolic blood pressures (SBP) and heart rate were moni-
tored at 6, 9 and 12 weeks of age in all animals by tail cuff
plethysmography (IITC, Inc., Model 20 cuff pump; Model 66
channel amplifier). Rats were acclimated to the recording
chambers (set at 27 degrees C) for approximately 15 minutes
before recording SBP. Approximately 10 recordings were
obtained from each rat and the mean of these measurements
was considered representative of the SBP of the individual
rat.
At 13 weeks of age, half of the rats from each group were
placed into metabolic cages, were allowed to acclimate for 3
days, and were monitored the following 3 days to determine
basal ad lib water intake and urine output. Water then was
CLOUGH. ARAVICH .4ND SLADEK
Control Female 4 77.0 1+_
7.4 0.60 t 0.06
NaCl Female ) 262.6 t 5.6 0.5x -r 0.08
MSCiFemale x 226.1 t 10.Y 1.71 5 o.1-3y
Control Male 5 43x.4 2 8.1 0.64 + 0.04
NaCl Male 9 440.3 -+ 6.8 0.65 i 0.03
MSG Male 7 352.6 -t 8.X I .oo t 0. I:!
Mean t S.E.M.
~rt.+.O5.
removed from the subjects in order to determine urine output
during the subsequent 48 hours of water deprivation.
One week after completion of water deprivation testing,
all animals were decapitated in a counter-balanced sequence
between 1000 and 1200 hours. Trunk blood was collected for
measure of plasma osmolality and hematocrit; serums were
assayed for AVP concentration by radioimmunoassay after
extraction (described below). Due to the possibility that food
intake may affect AVP release [2], animals were deprived of
food four hours prior to sacrifice. Brains were dissected im-
mediately and the hypothalamus from each brain was di-
vided into a dorsal (DH) and a ventral (VII) region contain-
ing the paraventricular hypothalamic (PVN) and supraoptic
hypothalamic (SON) AVP cell groups, respectively. Other
regions containing AVP terminals also were dissected includ-
ing the median eminence (ME) and the posterior pituitary
(PP). The hypothalamic and posterior pituitary dissection
procedures have been described previously (431. In addition
to these regions, a block of tissue was removed from the
dorsomedial medulla (DM) which contained the dorsal motor
nucleus of the vagus and portions of the nucleus and tractus
solitarius (collectively referred to as the dorsal vagal com-
plex, DVC). The DM tissue block also included the area
postrema and portions of the gracile, cuneate and vestibular
complexes.
Following removal, tissue blocks were placed in 2 ml mi-
crotubes containing 1 ml of ice-cold acetic acid (0.25%)
homogenized for 15 seconds and centrifuged. The superna-
tants were assayed for AVP by specific radioimmunoassay
(below). The anterior pituitary gland, adrenal glands,
gonads, and gonadal fat pads were removed and weighed at
autopsy.
All data were anaiyzed using r-tests, one-way analysis of
variance (ANOVA) or two-way ANOVAs. Post hoc multiple
comparisons following significant ANOVAs were performed
with Newman-Keuls tests at thepc0.05 level of significance.
The F scores for all significant ANOVAs are reported in the
text.
Serum was extracted using the acetone-ether method of
Robertson rt al. [38]. Extracts were frozen at -20C and
assayed for vasopressin content within two weeks. The per-
cent recovery from the extraction procedure was 67% for
each of 2 groups of serum samples extracted; all serum vas-
opressin values were corrected for extraction loss. Dupiicate
300 ~1 and single 150 ~1 aliquots of each serum extract were
MSG. BLOOD PRESSURE AND AVP
TABLE 2
WET WEIGHTOF POSTERlOR PITUITARY (PP). ANTERIOR PITUITARY (AP). GONADS
ADRENAL GLANDS (ADR) AT SACRIFICE
Group N PP (mg)
Control Female 4 1.08 2 0.14
NaCl Female 9 1.17 k 0.11
MSG Female 8 0.75 T 0.14
Control Male 5 1.38 f 0.16
NaCl Male 9 1.43 r 0.18
MSG Male 7 0.93 f 0.17
Mean k S.E.M.
*p<o.os.
c(n = 6).
assayed for AVP as previously described [42]. The antiserum
was generously provided by Drs. Jacques Durr and Marshall
Lindheimer (University of Chicago) [IS]. The assay has a
minimum sensitivity of 0.25 pglassay tube and a cross reac-
tivity with oxytocin of 0.001%. Interassay variation was
15.6%~
Tissue homogenate AVP content was determined utilizing
a different RIA. The antiserum used in this assay was devel-
oped in conjunction with Arnel Laboratories (New York,
NY), and has been described previously 1421. This assay has
a minimum sensitivity of I .O pg/assay tube and a cross reac-
tivity with oxytocin of less than 0.02%. Hypothalamic tissue
homogenates (VH-SON, DH-PVN, ME) were diluted 100
fold, PPs were diluted 10,000 fold and DM-DVC blocks were
not diluted. For all samples, duplicate 100 or 200 ~1 and
single 25 or 50 ru;laliquots were assayed. Due to a microcen-
trifuge malfunction, some of the brain homogenate samples
were lost prior to assay. The specific number of subjects
included in the various assay treatment conditions is shown
in the figures.
RESULTS
Male and female body weight and unilateral gonadal fat
pad weight were measured (Table 1). The MSG-treated rats
exhibited a significant degree of obesity as determined by
gonadal fat pad weight relative to body weight (female,
F(2,18)= 16.58; male, F(2,18)=4.9, p<O.Ol). Despite the ap-
pearance of obesity at sacrifice, MSG-treated animals of
both sexes were lower in overall body weight than either of
the control animal groups (female, F(2,18)=8.38; male,
F(2,18)=40.27, pcO.01). Signi~cant divergence of body
weight by MSG-treated animals from the control levels was
apparent as early as day 32 after birth (data not shown).
Endocrine gland weights at sacrifice were measured in
males and females (Table 2). The posterior pituitary gland
weights, although somewhat reduced, were not affected reli-
ably by MSG treatment blO.05). On the other hand, the
anterior pituitary glands (female, F(2,18)=46.9; male,
F(2,17)=12.9) and gonads (female, F(2,18)=3l.l; male,
F(2,18)=6. I) of male and female MSG-treated rats were sig-
nificantly lower in weight than the control glands @<O.Ol).
The adrenal glands of female MSG-treated rats were smaller
than those of the control rats, F(2,18)=18.79, p<O.Ol. The
adrenals of male MSG-treated rats, although tending to be
lower in weight, were not signi~~ntly different from the
53
(CON) AND
AP(mg) GON (Mg) ADR (mg)
12.13 ? 0.95 67.80 + 4.74 35.18 f 2.77
10.50 i 0.44 66.13 I 4.29 38.64 5 2.27
4.97 -t 0.45* 30.94 + 7.07* 22.41 2 1.33*
9.66 c 0.31 1.86 T!T0.07 30.32 2 2.26
9.32 i 0.64 I .83 i 0.11 29.76 + 2.61
5.55 i 0 ._59 1.42 i- o.ot3* 25.10 + 2.25
control adrenal weights @>0.05). In other studies, a statisti-
cally significant decrease in adrenal weight is reported in
both male and female rats administered MSG as neonates
[29,40].
Systolic blood pressure and heart rate of male and female
rats at 6, 9 and 12 weeks of age were measured (Fig. I). A
two-way ANOVA revealed a significant group difference in
SBP in female rats, F(3,18)=12.15, p<O.O005. Further
analysis of this main effect indicated that these values in the
MSG-treated female rats were significantly (p<O.OS) reduced
relative to the control and NaCl-treated groups. There also
was a significant overall age effect in the female rats,
F(2,36):= 17.18, p<O.OOOS, but no group-by-age interac-
tion effect @>O.OS). Thus, while female rats had reduced
SBP compared with controls, all groups exhibited a progres-
sive increase in SBP with age. In contrast to the female rats,
a two-way ANOVA of SBP in male rats was not associated
with a reliable group effect Q>O.OS), although there was an
overall age effect across groups. F(2,36)=5.02, p<O.O5,
which was similar to that seen across the female group. Male
rats also did not show a group by age interaction effect
@>0.05). Hence. unlike the female MSG-treated rats,
neonatal MSG administration failed to produce a consistent
reduction in SBP in male rats. Finally, no significant differ-
ences in heart rates were found across age or treatment
groups in either sex @>0.05).
Ad lib daily water intake was measured (Fig. 2). In abso-
lute amounts, the male MSG-treated rats consumed slightly,
though significantly, less water than the control rats,
F(2,8)=7.2; p<O.Ol. However, no significant differences
@>0.05) were observed between MSG-treated and control
rats when basal water intake was expressed as a function of
body weight. In addition, there were no reliabfe differences
between groups in plasma osmolalities or hematocrits at the
time of sacrifice (Table 3).
Absolute urinary output during the 48-hour water depri-
vation period also was measured (Fig. 3). A two-way
ANOVA revealed that both female (deprivation effect,
F(2.16)~ 107.9, p<O.OOl) and male (deprivation effect,
F(2,16)- 178.2, p<O.OOl) rats progressively reduced urine
output in response to increasing hours of water deprivation.
Within each sex, MSG treatment failed to influence differen-
tially the effects of water deprivation on urine output
tnonsigni~cant group and group-by-depl-ivation effects).
Likewise, no differences were found between groups when
urine output was expressed as a function of body weight

Female
FIG. 1. Systolic blood pressure and heart rate of female and male rats at 6, 9 and t2 weeks of age. The number of animals per
group is: female controls, 4; female MSG, 8; female and male NaCl, 9; male control, 5: male MSG, 7. *There was a consistent
reduction (p<O.OS) in SBP in the female MSG rats across the various ages. Mean2S.E.M.
(data not shown). Therefore, the ability to reduce urine out-
put in response to water deprivation was not affected by
MSG treatment.
The AVP content in brain region homogenates and
serums from female and male rats were measured (Figs. 4
and 5, respectively). Statistical comparisons revealed no
significant group differences (p>O.O5) within either sex in
AVP content of the VH-SON, DH-PVN, PP, ME and the
DM-DVC. As with the various brain regions, serum AVP
levels did not differ between groups in either sex @>0.05).
DISCUSSION
This investigation confirms several previous findings of
the MSG Obesity Syndrome [311 and provides new data
regarding neurohypophyseal AVP and hemodynamic func-
tion.
We found that neonatal MSG-treatment resulted in obe-
sity, judged by relative gonadal fat pad weights, hypo-
gonadism, reduced anterior pituitary gland weights and
reduced adrenal weights (in male rats, however, p>O.OS).
Thus, the animals in this experiment exhibited the classic
features of the MSG toxicity syndrome [i, 6, 9, 19, 29, 36,
37, 401.
In contrast to MSGs effects on anterior pituitary function
129,401, the neurotoxin had no effect on the content of AVP
in SON, PVN, DVC, PP, ME or serum. While this conclu-
sion is baaed on limited samples in some groups, the present
regional microdissection results are consistent with previous
findings obtained from whole hypothalami and whole pitui-
tary homogenates [21]. The serum AVP analysis also is con-
sistent with the results of Knepel et ul. [21], but fails to
CLOUGH. ARAVICH AND SLADEK
D ..a Control
c---+ NaCl
- MSG
6 9 12
Age (weeks)
support the claim of Van Den Buuse et al. [46], that neonatal
MSG treatment produces higher levels of serum AVP in
adult rats. Thus we conclude that, under basal conditions,
neither the magnocellular AVP projection system to the
neurohypophysis nor the parvocellular AVP projection sys-
tem to the DM is altered by neonatal MSG treatment.
It is possible that the functional controf of AVP release
may be altered by neonatal MSG treatment, even though
regional AVP content is unaffected under basal conditions.
The circumventricular organs play an important role in the
regulation of AVP release [27, 28, 441 and are damaged by
neonatal MSG treatment 1241. Therefore, the functional
status of the vasopressinergic system was examined in the
present experiment. Monosodium glutamate-treated rats
demonstrated normal basal water intake and urine output,
and displayed a normal capacity to decrease urine output in
response to water deprivation. There was no indication of
abnormalities in the antidiuretic response of MSG-treated
rats to chronic dehydration. Plasma hematocrit and osmolality
also were found to be within normal limits at the time of sac-
rifice. These data support the conclusion that AVP release in
response to dipsogenic stimuli such as hypertonic saline [25] or
water deprivation (present study) is not altered by neonatal
MSG treatment. The selective effects of MSG on other
stimuli to AVP release [25] indicate that MSG-induced toxi-
city has differential effects on the varied mediators of AVP
release.
Unlike the lack of effect of MSG on the AVP system,
female MSG-treated rats had significantly lower SBP com-
pared with the control and NaCI-treated groups. Although
there appeared to be a transient reduction in SBP of male
rats at 9 weeks of age, male SBP was not statisticaHy altered
MSG, BLOOD PRESSURE AND AVP 55

TABLE 3
PLASMA OSMOLAL~TIES fPOsmf AND HEMATOCRITS (%Hct) IN
FEMALE AND MALE RATS

POsm
Group N mosmoVkg Hz0 % Hct

Control Female 4 296.3 c 2.7 41.25 2 1.36

NaCI Female 9 298.2 2 1.8 43.28 r 0.91
MSG Female 8 298.9 2 3.0 42.42 2 0.66
Control Male 5 301.0 + 2.37 48.28 + 0.94
NaCl Male 9 300.5 * 1.31 46.32 + 0.91
MSG Male 7 300.8 2 1.57 47.27 2 0.51

Mean 2 S.E.M.
Female

Female

9
1 15
9
z
._
3
1C
f
B
Male
5
FIG. 2. Twenty-four-hour water intake in absolute terms and rela-
tive to body weight in female and male rats. The number of animals
per group is indicated over the co~esponding column. Male MSG-
treated rats consumed less water than NaCl or NaCi-treated rats in C
absolute terms @<O.OS) however when corrected for body weight
there were no significant differences. Mean+S.E.M. Solid column:
Male o- - -a Colltrd
control; striped column: NaCI; dotted column: MSG.
O--Q NaCl
O---O MSG
2c

by MSG treatment. These data are in contrast with a previ-

ous report that neonatal MSG treatment lowered SBP in
male WKY and SHR rats (females were not studied) [46]. It 2 15
should be noted, however, that Sprague-Dawley rats differ in
several respects from SHR and WKY rats (e.g., [17]), and B
that there may be strain differences in the sensitivity to
neonatal MSG toxicity.. (Ser notr &deed in prcmf~) Regard- p 10

less, the failure of MSG to consistently reduce SBP in the si

male rats of the present study may reflect a gender-specific i?
difference in sensitivity to the neurotoxic effects of MSG on
x 5
SBP. As mentioned previously, other gender-specific effects
of MSG have been described 14, 5, 14, 291.
Monosodium glutamate-induced hypotension in femaies
may be related to selective damage of one or more CNS 0
area(s) involved in cardiovascular homeostasis. In the hypo- 0 24 48
thalamus, the periventricular tissue anterior to the third ven-
liours of Water Deprivatt
tricle (AV3V) [7] and the paraventricular nuclei are involved
in blood pressure regulation [41]. At least some areas of the FIG. 3. Twenty-four-hour urine output (ml) during 48 hours of acute
AV3V region are susceptible to damage by neonatal MSG water deprivation in female and male rats. The number of rats per
1241and, due to the gender-specific nature of the hypotensive group is the same as the corresponding groups depicted in Fig. 2.
effect in Sprague-Dawley rats, it is of particular interest that Mean?S.E.M.
 CLOUGH. ARAVICH AND SLAUEK

T i
180
I

WJ

I40

120

loo

80

60

43

16

W-SON OH-PVN DM-DVC ME PP

FIG. 4. AVP content of female ventral hypothalamic-supraoptic nuclei (VH-SON), dorsal hypothalamic-paraventricular
nuclei (DH-PVN), dorsal medulla-dorsal vagal complex (DM-DVC), median eminence (ME), posterior pituitary (PP)
homogenates and serum. The number of animals per group is indicated over the corresponding column. Mean2S.E.M.
Columns same as Fig. 2.

W-SON OH-PVN DM-OVC ME PP Serum

FIG. 5. AVP content of male ventral hypo~~amic-supraoptic nuclei (VH-SON), dorsal hypothalamic-p~ra~ent~cu~ar
nuclei (DH-PVN), dorsal medulla-dorsal vagai complex (DM-DVC), median eminence (ME), posterior pituitary (PP)
homogenates and serum. The numbers of animals per group is indicated over the corresponding column. Mean2S.E.M.
Colunks same as Fig. 2.

the AV3V region exhibits a variety of anatomical and neuro-
chemical sex differences in rats [3,11]. Brainstem structures
represent additional possible loci of the MSG effect on blood
pressure in females. There have been descriptions of MSG-
induced lesions in the DM [24,33], an area known to partici-
pate in cardiovascular regulation [4If. While lesions of the
AV3V, hypothalamus and DM may contribute to the ob-
served hypotension in MSG-treated females, this effect ap-
pears to be unrelated to changes in neural AVP.
Circulating sex steroids have also been implicated in the
control of blood pressure in rats [lo]. However, the sex
steroids do not seem to have contributed to MSG-induced
hypotension in the female rats in the present study. While it
is clear that MSC-treated female rats exhibit severe ovarian
dysgenesis and maintain a greatly reduced serum estradiol
concentration compared to controls {30], gonadectomy in
female hypertensive rats increases [I31 or has no effect ilOJ
on blood pressure. The androgens, on the other hand, have
been implicated in the pathogenesis of some forms of hyper-
tension. Supporting this view, gonadectomy can red,uce
blood pressure in male hypertensive rats [lo]. Qespite the
fact that the male MSG-treated rats in the present study were
hypogonadal and presumably had markedly reduced serum
testosterone concentrations 1301, they were not hy~ot~nsivc
relative to controls. Thus, based on the available data, it
appears unlikely that the sex difference in MSG-induced
hypotension is a consequence of the effects of MSG on cir-
culating gonadal steroids.
Finally, an alteration in the renin-angiotensin-aldosterone
system (RAAS) also could contribute to the observed
hypotension in MSG-treated female rats. In the present
study, overall adrenal gland weights were reduced reliably in
female but not in male rats. Therefore, the RAAS may be
compromised in female rats. However, male adrenal gland
weights are consistently reduced in other MSG studies
[29,40] and tended to be reduced in the present study. In
MSG, BLOOD PRESSURE AND AVP 51

addition, blockade of the RAAS in salt-repleted normotensive
animals does not, in and of itself, reduce blood pressure 1231.
In summary, the present investigation reveals that the
AVP content of the posterior pituitary, hypothalamus and
lower brainstem is resistant to the neurotoxic effects of
neonatal MSG in rats, and that MSG has little influence on
antidiuresis to chronic dehydration. In contrast, MSG exerts
a sexually dimorphic hypotensive effect in female
Sprague-Dawley rats, which is not associated with a com-
pensatory elevation in heart rate or circulating AVP concen-
tration. These observations suggest that baroreflex mech-
anisms have been reset in MSG-treated female rats to main-
tain blood pressure at a lower level, and that this resetting of
the baroreflex mechanism occurs independent of any central
or peripheral vasopressin changes.
ACKNOWLEDGEMENTS
This work was supported by grants ROl-HL-28172 and
ROI-AM-19761 from the United States Public Health Service
(C.D.S.), and by National Research Service Awards 1 F32 MH-
09136 (R.W.C.) and 1 F32 MH-08872 (P.F.A.). We are grateful to
Ms. Carol Sterling for her laboratory assistance and to Dr. Michael
Mangiapane for his comments on the manuscript.

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Note Added in Proofi Unlike the findings of [46], it has now

been reported that, under basal conditions, neonatal MSG
treatment has no effect on the SBP of male SHR and WKY rats
(Mosqueda-Garcia, R., R. Eskay, N. Zamir, M. Palkovits and
G. Kunos. Opioid-mediated cardiovascular effects of clonidine
in spontaneously hypertensive rats: elimination by neonatal
treatment with monosodium glutamate. ~~d~~e~i~~~~g~ 118:
3814-1822, 1985). Once again, female rats were not examined.