SOCIAL ISOLATION INDUCES DEPRESSIONLIKE BEHAVIORS AND AUTONOMIC DYSFUNCTION IN SOCIALLY MONOGAMOUS P

1
SOCIAL ISOLATION INDUCES DEPRESSION-LIKE
BEHAVIORS AND AUTONOMIC DYSFUNCTION IN SOCIALLY
MONOGAMOUS PRAIRIE VOLES ANGELA J. GRIPPO, C. SUE
CARTER, STEPHEN W. PORGES DEPT. PSYCHIATRY AND
BRAIN-BODY CENTER, UNIV. ILLINOIS CHICAGO
INTRODUCTION
SUMMARY
STRESSOR RESPONSES
BEHAVIOR

• The experiments described here show that social
  isolation in prairie voles induces
• A reduction in sensitivity to a rewarding
  stimulus (i.e., anhedonia)
• Increased resting HR and decreased resting HR
  variability
• Increased HR reactivity to a novel social
  stressor (resident-intruder test) and longer
  recovery time to pre-stressor HR values
  following the stressor
• Significantly reduced parasympathetic tone to
  the heart

Previously we have described several important
cardiac changes in a rodent model of depression,
including elevated heart rate (HR), reduced HR
variability, and elevated sympathetic tone 2.
It is possible that social interactions may have
an impact on both mental health and
cardiovascular health.
Social isolation led to anhedonia (reduced
sucrose intake) relative to respective baseline
values and those of paired animals (Figure 2).
During the resident-intruder test isolated
animals displayed an exaggerated HR response
relative to paired animals, but total activity
level during the stressor did not differ between
the two groups (Figure 5). The time to recovery
of HR (to pre-stressor values) was significantly
longer in isolated animals, compared to paired
animals (Figure 6).
Figure 2. Mean ( SEM) water and sucrose intake
at baseline and following 2 and 4 weeks of social
isolation in paired and isolated prairie voles.
For sucrose intake P lt 0.05 vs. respective
paired value P lt 0.05 vs. respective baseline
value.
The prairie vole is a small rodent species
(Figure 1) that exhibits social interactions
unlike other rodents but similar to primates,
including living in family groups and forming
adult pair bonds 1.
Figure 1. Two prairie voles.
B
A
Because the prairie vole displays unique social
behaviors, it may be a valuable model for
studying the role of the social environment in
mediating behavior and cardiovascular regulation.
This will provide a greater understanding of the
association between mental health (i.e.,
depression) and cardiovascular health (i.e.,
heart disease). The current study describes the
effects of social isolation on the behavior and
physiology of prairie voles. The findings
indicate that social isolation induces
depression-like behaviors as well as
cardiovascular dysfunction that is consistent
with characteristics related to heart disease.
ECG RESPONSES
CONCLUSIONS
Figure 5. Mean ( SEM) HR (Panel A) and total
activity level (Panel B) during a 5-minute
resident-intruder test in paired and isolated
prairie voles. P lt 0.5 vs. paired value.
Social isolation induced an elevation in resting
HR and a reduction in resting HR variability
(Figure 3).
Chronic social isolation may be a stressor in
socially monogamous prairie voles that leads to
altered behavior and cardiac function. Isolated
prairie voles display both behavioral signs of
depression and altered cardiac and autonomic
profiles, including increased HR and reduced HR
variability, exaggerated reactivity to a novel
stressor, and a reduction of vagal tone to the
heart. Behavioral and physiological responses to
negative social stressors may play a mechanistic
role in the link between signs associated with
mood disorders and cardiovascular dysfunction.
The current results provide insight into this
important association.
A
B
PROCEDURES
Figure 6. Mean ( SEM) time to recovery to
pre-stressor HR values following a 5-minute
resident-intruder test in paired and isolated
prairie voles. P lt 0.5 vs. paired value.
Preparation Radiotelemetry transmitters were
implanted intraperitoneally into adult female
prairie voles for the recording of
electrocardiogram (ECG). Following 5 days of
recovery in divided cages, animals were returned
to the home cage with a same-sex sibling and
allowed to recover for an additional 5-7 days.
Social Isolation Following a period of baseline
ECG recordings, animals were either isolated from
the sibling or remained paired for 4 weeks. ECG
was recorded continuously during this period and
during all behavioral and physiological tests.
Sucrose Intake Sucrose intake was used as an
index of anhedonia (reduced responsiveness to a
pleasurable stimulus a characteristic found in
human depressed patients), and was measured prior
to and following 2 and 4 weeks of social
isolation. Pharmacological Autonomic
Blockade Autonomic inputs to the heart were
selectively blocked following 4 weeks of
isolation with atenolol 8 mg/kg ip b-adrenergic
receptor (sympathetic) blockade, atropine 4
mg/kg ip cholinergic receptor (parasympathetic)
blockade, or both drugs combined autonomic
blockade. ECG data were recorded continuously
for several hours, and the resultant changes in
HR were calculated. Social Stressor
Exposure Animals were exposed to an acute social
stressor, the resident-intruder test, following 4
weeks of social isolation or pairing.
Figure 3. Mean ( SEM) HR (Panel A) and HR
variability (Panel B) in paired and isolated
prairie voles at baseline and following 4 weeks
of social isolation. P lt 0.05 vs. paired value.
REFERENCES
PHARMACOLOGICAL AUTONOMIC BLOCKADE
1 Carter CS, DeVries AC, Getz L. Physiological
substrates of mammalian monogamy the prairie
vole model. Neurosci Biobehav Rev 19 303-314,
1995. 2 Grippo AJ, Moffitt JA, Johnson AK.
Cardiovascular alterations and autonomic
imbalance in an experimental model of depression.
Am J Physiol 282 R1333-R1341, 2002.
Social isolation led to a significant reduction
of parasympathetic tone, relative to social
pairing (Figure 4).
B
A
Figure 4. Mean ( SEM) absolute HR (peak
response Panel A) and change in HR from baseline
(Panel B) in paired and isolated prairie voles
during b-adrenergic receptor blockade with
atenolol, cholinergic receptor blockade with
atropine, and combined autonomic blockade with
both drugs. P lt 0.05 vs. respective paired
value.

• The authors would like to thank Damon Lamb for
  technical assistance
• This research was supported by MH-73233 (Grippo),
  HD-38490 (Carter), and MH-67446 (Porges)
• Contact Angela Grippo with comments or questions
  agrippo_at_psych.uic.edu