Transgenerational Effects of Social Environment on Variations in Maternal
Care and Behavioral Response to Novelty
Frances A. Champagne
Michael J. Meaney
Cross-fostering studies in the rat have illustrated the importance of the postnatal environment in
mediating the transmission of maternal licking/grooming (LG) from mother to offspring. The authors
addressed the question of how postweaning social conditions can alter the patterns of maternal behavior.
Juvenile female offspring of high LG and low LG mothers were placed in either standard, enriched, or
impoverished postweaning environments for 50 consecutive days and then mated and observed with their
own litters. Analysis of LG behavior indicated that the effect of postweaning environment was dependent
on the level of postnatal mother–infant interaction. Postweaning isolation reduced exploratory behavior,
maternal LG, and oxytocin receptor binding in the offspring of high LG mothers, whereas social
enrichment enhanced exploration, LG behavior, and oxytocin receptor binding of low LG offspring.
These effects were also transmitted to the next generation of offspring. Thus, maternal LG and the neural
mechanisms that regulate this behavior exhibited a high degree of plasticity in response to changes in
environment both within and beyond the postnatal period, with implications for the transmission of
behavioral response to novelty and maternal care across generations.
Keywords: maternal behavior, oxytocin, environment, transgenerational
Mother–infant interactions occurring early in development have
a profound impact on offspring physiology and behavior. In pri-
mates and humans, reduced levels of maternal care, either in the
form of complete maternal deprivation or of neglect, have been
shown to increase stress responsivity, impair cognitive ability, and
reduce social behavior (Arling & Harlow, 1967; Carlson & Earls,
1997; Glaser, 2000; Harlow, Dodsworth, & Harlow, 1965; Trickett
& McBride-Chang, 1995). Likewise, in rodents, complete mater-
nal deprivation or extended periods of mother–infant separation
also affected response to stress, cognition, and juvenile and adult
social interactions (Kalinichev, Easterling, Plotsky, & Holtzman,
2002; Lehmann, Pryce, Bettschen, & Feldon, 1999; Lovic, Gonza-
lez, & Fleming, 2001). Conversely, postnatal handling involving
brief periods of maternal separation, which stimulate maternal care
(Liu et al., 1997), decreased the stress response of offspring and
enhanced learning and memory (Meaney, Aitken, Bhatnagar, &
Sapolsky, 1991; Meaney, Aitken, Bodnoff, Iny, & Sapolsky,
1985). These studies have highlighted the importance of the post-
natal period in shaping adult phenotype and the potential role of
maternal care in mediating these long-term effects.
Direct evidence for the role of maternal care in mediating
offspring phenotype has emerged from studies of the impact of
natural variations in maternal behavior. In both primates and
rodents, females have exhibited stable individual differences in
maternal care that can be quantified and associated with develop-
mental outcomes (Champagne, Francis, Mar, & Meaney, 2003;
Fairbanks, 1989; Fairbanks & McGuire, 1988; Meaney, 2001). In
rodents, natural variations in maternal licking/grooming (LG) of
pups during the first week postpartum have been observed that
alter gene expression, physiology, and behavior of both male and
female offspring (Caldji et al., 1998; Francis, Diorio, Liu, &
Meaney, 1999; Liu et al., 1997). Offspring of mothers who en-
gaged in high levels of LG had increased levels of hippocampal-
glucocorticoid receptor expression, an attenuated hypothalamic–
pituitary–adrenal response to stress, and enhanced performance on
measures of cognitive ability (Caldji et al., 1998; Liu, Diorio, Day,
Francis, & Meaney, 2000; Liu et al., 1997). Cross-fostering of the
biological offspring of high LG mothers to low LG mothers and
the offspring of low LG mothers to high LG mothers has illustrated
that the adult phenotype of these offspring is shaped by the quality
of postnatal care received (Francis et al., 1999). Moreover, these
variations in maternal care are passed from one generation to the
next such that the female offspring of high LG mothers exhibit
high levels of LG toward their own offspring (Champagne, Fran-
cis, et al., 2003, Francis et al., 1999), providing a behavioral
mechanism of inheritance of stress responsivity and social behav-
ior (Champagne & Curley, 2005).
The transmission of maternal LG across generations is associ-
ated with the levels of neuropeptide receptors in the medial pre-
optic area of the hypothalamus (MPOA). Oxytocin receptor (OTR)
binding is elevated in the MPOA of high LG compared to low LG
females, and infusion of a highly selective OTR antagonist on
postpartum Day 3 reduces levels of LG among high LG females
and abolishes group differences in LG (Champagne, Diorio,
Sharma, & Meaney, 2001; Francis, Champagne, & Meaney, 2000).
Frances A. Champagne, Department of Psychology, Columbia Univer-
sity; Michael J. Meaney, McGill Program for the Study of Behavior, Genes
and Environment and Developmental Neuroendocrinology Laboratory,
Douglas Hospital Research Centre, McGill University, Montreal, Quebec,
Correspondence concerning this article should be addressed to Frances
A. Champagne, Columbia University, Department of Psychology, 406
Schermerhorn Hall, 1190 Amsterdam Avenue, New York, NY 10027.
CORRECTED FEBRUARY 21, 2008; SEE LAST PAGE
2007, Vol. 121, No. 6, 1353–1363
Copyright 2007 by the American Psychological Association
0735-7044/07/$12.00 DOI: 10.1037/0735-7044.121.6.1353
Offspring of low LG mothers have reduced estrogen-sensitivity in
the MPOA, associated with decreased levels of estrogen receptor
alpha (ER?) expression in this region when compared to offspring
of high LG mothers (Champagne et al., 2006; Champagne,
Weaver, Diorio, Sharma, & Meaney, 2003). Estrogen and ER?
exert potent regulatory effects on OTR expression, acting through
genomic and nongenomic mechanisms to increase OTR levels
(Bale, Davis, Auger, Dorsa, & McCarthy, 2001; Breton & Zingg,
1997; Zingg et al., 1998). Thus, differential levels of LG regulate
offspring’s levels of ER? mRNA in the MPOA and serve as a
potential mechanism for the variations in OTR binding that have
been observed in estrogen-primed female offspring of high com-
pared to low LG mothers.
These studies have suggested that social interaction during the
early postpartum period is critical in regulating the maternal be-
havior of offspring and thus in generating the transmission of
maternal care across generations. The critical question addressed
in the current study is whether social interactions beyond the
postnatal period can alter patterns of maternal care and thus alter
generational transmission. Few studies have examined the impact
of postweaning social isolation and social enrichment (housed in
same-sex, same-age groups) on maternal behavior in the rat (Gen-
aro & Schmidek, 2002), however, the offspring of females reared
in these environments “inherit” the phenotype characteristic of rats
housed under these conditions (Dell & Rose, 1987; Kiyono, Seo,
Shibagaki, & Inouye, 1985; McKim & Thompson, 1975). Both the
biological and foster offspring of female rats raised in socially
enriched environments spend more time exploring a novel envi-
ronment and require fewer trials to learn to bar press for reinforce-
ment when compared to females raised in impoverished environ-
ments (Dell & Rose, 1987). Maze learning is also enhanced in the
male offspring of enriched females (Kiyono et al., 1985). These
findings suggest the possibility that the female’s behavior toward
her offspring or her reproductive physiology is altered, thus re-
sulting in a generational transmission of postweaning effects.
The present study is an investigation of the plasticity of maternal
behavior in response to social cues experienced during both the
postnatal and postweaning periods and how these experiences alter
the phenotype of subsequent generations of offspring. To examine
this issue, at weaning we placed the female offspring of high and
low LG mothers in standard, enriched, and impoverished environ-
ments. We can reliably predict the maternal phenotype and hypo-
thalamic OTR binding of these offspring on the basis of the quality
of the postnatal care received, however the question is whether the
quality of social interaction beyond this period can alter the pre-
dicted behavioral and neuroendocrine patterns. In addition, we
assessed the effects of these conditions on behavior response to a
novel environment as well as the impact of mothers’ prenatal and
postweaning environment on subsequent offspring maternal care
and exploratory behavior.
Materials and Method
The subjects were Long–Evans hooded rats born in our colony
and housed in 46 cm ? 18 cm ? 30 cm Plexiglas cages with food
and water provided ad libitum. The colony was maintained on a
12-hr light–dark cycle with lights on at 0800. Routine cage main-
tenance began on Day 7 of life, and rats were otherwise unma-
nipulated. All procedures were performed according to guidelines
developed by the Canadian Council on Animal Care and protocols
approved by the McGill University Animal Care Committee. One
week prior to parturition and throughout lactation, adult females
were housed singly.
Adult Long–Evans females (n ? 40) from the Douglas Hospital
Research Centre colony were singly housed, mated, and observed
during the first 6 days postpartum. From these, nine low LG litters
(M ? 8.8%, SD ? 0.11) and seven high LG litters (M ? 13.8%,
SD ? 0.21) were selected for the study. At weaning on Day 21, 3
to 7 female pups were selected from each litter and then weighed
and placed in standard, impoverished, or enriched housing (n ? 12
low LG pups, n ? 12 high LG pups per housing condition). Under
impoverished housing conditions, pups were singly housed in 22
cm ? 18 cm ? 22 cm cages with wire mesh floors. Under
standard housing conditions, pups were pair housed in same-sex,
same-litter groups in 46 cm ? 18 cm ? 30 cm Plexiglas cages
containing bedding material. Under enriched housing conditions,
offspring were weaned into a multilevel, six-compartment steel
cage with a wire mesh floor. Each 50 cm ? 60 cm ? 50 cm
compartment was joined to adjacent compartments with tunnels
through which rats could move freely between levels and com-
partments. Toys were placed in each of the compartments. These
consisted of plastic and wooden blocks, tennis balls, plastic tubing,
bells, and plastic cars. The location of the toys was altered each
week. Though there are many stimulating aspects of this environ-
ment, previous studies have indicated that it is the social interac-
tion made possible in this housing condition that is critical for
inducing behavioral changes (Morgan, 1973). Due to restrictions
on the number of rats that could be placed in this apparatus, only
offspring of high and low LG dams were included in this study.
After spending 50 days in the specified housing condition, females
were removed, weighed, singly housed into standard Plexiglas
cages, mated, and placed in the observation room. Following
parturition and after 6 days of maternal observation, 5 females
from each of the six conditions (low LG/standard housed, high
LG/standard housed, low LG/impoverished, high LG/impover-
ished, low LG/enriched, high LG/enriched) were decapitated, and
their brains were extracted for OTR binding assay. The remaining
7 females per group and their litters were left undisturbed, with the
exception of routine cage maintenance, until weaning. At Day 21,
14 male and 14 female offspring from each condition were weaned
into standard housing. This generation would thus be the grand-
offspring of high and low LG dams whose mothers were housed
under the three social conditions. Two weeks postweaning, dams
were tested in the open-field and object-recognition tests. Male
offspring of these dams were, as adults (Day 90), also tested in the
open-field and object-recognition tests. Female offspring were not
tested in the open-field and object-recognition tests to avoid the
potential effects of the manipulation involved in testing on mater-
nal behavior but were instead mated at Day 70 and observed with
their litters for 6 days postpartum. Thus, none of the females
included in this study were tested prior to mating. To address the
potential influence of litter effects, we used litter as a covariant
within all analyses of variance (ANOVAs) of the data.
CHAMPAGNE AND MEANEY
Assessment of Postpartum Maternal Behavior
Maternal care was assessed during Days 1 to 6 postpartum
through observations of home-cage mother–infant interactions as
previously described (Champagne, Francis, et al., 2003). Dams
were not disturbed for the duration of the 6-day observation period.
Each day consisted of five observation periods (0600, 1000, 1300,
1700, 2100), 72 min in duration. Within each observation period,
the behavior of each mother was scored every 3 min (25 observa-
tions/period ? 5 periods/day ? 125 observations/mother/day) for
the following behaviors (also described in Myers, Brunelli, Squire,
Shindeldecker, & Hofer, 1989): mother not in contact with pups,
mother carrying pup, mother licking and grooming any pup (both
body and anogenital licking were included), and mother nursing
pups. Nursing posture was rated as either (a) an arched-back
posture when the mother was arched over pups with legs extended,
(b) a “blanket” posture in which the mother lays over the pups with
no leg extension, or (c) a passive posture in which the mother is
lying either on her back or side while the pups nurse. Observers
were trained to a high level of interrater reliability (i.e., ?0.90).
The selection of rats as high or low LG mothers was based on
the mean and standard deviation for this measure for the maternal
cohort. The characterization of individual mothers thus depended
upon the reliability of the cohort data set. To provide more reliable
estimates of individual differences in maternal behavior, we ob-
served cohorts of approximately 40 mothers/litters. The size of this
cohort was also determined by the observational procedure. One
individual can accurately observe the behavior of as many as 40
rats with sequential observations within a 3-min time span. High
LG mothers were defined as females whose mean frequency scores
for LG over Days 1 to 6 postpartum were greater than 1.0 standard
deviation above the mean. Low LG mothers were defined as
females whose mean frequency scores for LG over Days 1 to 6
postpartum were greater than 1.0 standard deviation below the
mean. LG data from multiple cohorts of females indicated that
mean and standard deviation did not differ significantly between
For the analysis of levels of postpartum OTR binding, lactating
females were rapidly decapitated on postpartum Day 6. Brains
were extracted, placed briefly in isopentane, and kept at ?80 °C
until processed. Brains were sectioned in the coronal plane at 16
?m, and sections thaw mounted onto poly-L-lysine coated slides
that were stored at ?80 °C until the assay was performed. We
processed slide-mounted coronal brain sections for receptor auto-
OVT; New England Nuclear, Boston, MA) as previously described
(Champagne et al., 2001; Francis et al., 2000).125I-OVT has a very
high affinity for OTRs (Kd? 0.048 ? 0.008 nM) and a 10-fold
greater affinity for OTRs than oxytocin (Elands et al., 1988). The
affinity of this compound for OTRs is approximately 300-fold
higher than it is for V1 and V2 vasopressin receptors (Elands et al.,
1988). After a prewash in Tris-HCl (pH ? 7.4), slides were
exposed to a 75-min incubation (at room temperature) of 60 pM
125I-OVT in Tris with MgCl (10 mM), bovine serum albumin
(0.1%), and bacitracin (0.05%). Nonspecific binding was defined
in adjacent sections by adding 50 nM Thr4Gly7-oxytocin (a con-
centration previously found to completely displace 60 pM125I-
OVT; Elands et al., 1988) to the incubation buffer. The final
35-min wash was performed at room temperature in 50 mM Tris
(pH ? 7.4), 100 mM MgCl to reduce background. After air-
drying, the slides were exposed to BioMax MR film (Kodak) for
included in the cassette for quantification.
Using an image-capture system (http://www.imagingresearch
.com, Imaging Research, St. Catherines, Ontario), we analyzed
autoradiograms with MCID software. Three sections were ana-
lyzed bilaterally at each level. For each rat, total and nonspecific
binding was measured for each region and the difference taken to
yield specific binding. Specific binding was greater than 90% of
total binding. The statistical analysis was performed on the mean
of these values for each rat by brain region according to the atlas
of Paxinos and Watson (1986).
125I-OVT autoradiographic standards (Amersham) were
The open-field test is a standard tool for measuring behavioral
aspects of anxiety in rodents (Archer, 1973; Belzung & Griebel,
2001; Crawley, 1985). The open field itself serves as a novel
environment for the rat. Habituation to this environment is typi-
cally followed by exploratory behavior, operationally defined as
increased entries into the inner area of the field. The open field
used was a 120 cm ? 120 cm wooden box. The behavior of the rat
in this field was recorded with a video camera mounted on a tripod
adjacent to the field. We completed the coding of these video
recordings using a DOS-based program designed to give summa-
ries of the amount of time spent in the inner and outer area of the
field, as well as the overall activity of the rat. On the day of testing,
the rat was removed from its home cage and placed directly into
one corner of the open field. After a 10-min session, the rat was
removed and returned to its home cage. All testing was conducted
under standard lighting conditions. During analysis of the record-
ings, the field was divided into a grid of 8 ? 8 squares. Exploration
was defined as the time spent in the inner 6 ? 6 squares, whereas
overall activity was defined as the number of squares crossed
during the 10-min session.
The object-recognition test is a cognitive measure that has been
used to detect memory impairments (Ennaceur & Aggleton, 1994;
Ennaceur & Delacour, 1988). The test is designed to compare the
amount of exploration of a novel object relative to that of an object
identical to one that the animal has already been exposed to
(discrimination ratio). The objects in this case differ in color and
shape. The testing apparatus used was a black 75 cm ? 75 cm
wooden box containing bedding material (approximately 2-cm
deep). The behavior of the rat in this box was recorded with a
video camera mounted on a tripod adjacent to the box. Prior to the
day of testing, rats were habituated to this testing apparatus and the
process of being removed from their home cage. This aspect of the
procedure was designed to reduce stress-related behaviors in this
novel environment. There were 3 days of habituation trials. Each
day, the rat was removed from the home cage and placed in the
testing apparatus for 5 min. After the session, the rat was returned
to the home cage. On the 4th day, the rat was placed in the testing
EFFECTS OF ENVIRONMENT ON MATERNAL CARE
apparatus for 5 min with two identical objects. After a 15-min
delay, the rat was returned to the apparatus. During this session,
two new objects were placed in the apparatus; one identical to the
two objects in the first session (the old object), and one new object.
This session was 5 min in duration. To ensure that discrimination
ratios were not affected by a preference for the physical charac-
teristics of either the new or the old object, we used a counterbal-
Weaning weight and weight after 50 days in the specified
housing condition did not differ as a function of maternal pheno-
type or housing condition. Day 50 weights for offspring of low LG
dams were 321.8 ? 5.2 g for standard housed, 319.0 ? 4.3 g for
impoverished, and 322.1 ? 4.6 g for enriched females and, for
offspring of high LG dams, 317.9 ? 6.1 g for standard housed,
319.7 ? 4.9 g for impoverished, and 323.2 ? 5.1 g for enriched
females. Under standard housing conditions, 91.7% (11/12) of
both high and low LG offspring gave birth. Among females placed
in impoverished housing conditions, 83.3% (10/12) of low and
75.0% (9/12) of high LG offspring gave birth. Enrichment housing
resulted in a birth rate of 91.7% (11/12) for low LG offspring and
a 100.0% (12/12) birth rate in high LG offspring. Only females
who successfully gave birth were included in subsequent behav-
Maternal Behavior of Standard Housed, Impoverished,
and Enriched Females
Two-way ANOVA (Group ? Housing Condition) of LG be-
havior of female offspring of high and low LG mothers indicated
a significant main effect of housing, F(2, 67) ? 13.4, p ? .001,
and a significant Group ? Housing Condition interaction, F(2,
67) ? 4.0, p ? .05. Tukey post hoc analysis revealed a significant
difference in LG behavior between offspring of high LG and low
LG females housed under standard conditions (p ? .05), however,
no group differences were observed between females exposed to
impoverished and enriched conditions (see Figure 1). Offspring of
high LG females housed in impoverished conditions showed sig-
nificant decreases in LG compared to high/standard housed fe-
males (p ? .05). Conversely, offspring of low LG females housed
in enriched conditions showed elevated levels of LG compared to
low/standard housed females (p ? .001). Impoverished housed
offspring of low LG females and enriched housed offspring of high
LG females showed no changes in LG relative to same-group
females housed in standard conditions. No group or housing ef-
fects were observed on any other aspect of maternal behavior.
Exploration and Activity of Standard Housed,
Impoverished, and Enriched Females
Following observation of maternal behavior 2 weeks postwean-
ing, we observed dams for 10 min in the open-field test, and group
comparisons were made of time spent in the inner-field area
(exploration; see Figure 2) and total squares crossed during testing
(activity). Two-way ANOVA of exploratory behavior indicated a
main effect of group, F(1, 30) ? 12.9, p ? .001; a main effect of
housing, F(2, 30) ? 12.1, p ? .001; and a significant Group ?
Housing Condition interaction, F(2, 30) ? 10.3, p ? .001. Post
hoc analysis indicated a significant difference between standard
housed offspring of high and low LG females (p ? .001), with
high LG females being more exploratory. Female offspring of high
and low LG females placed in impoverished housing did not differ
from each other in exploratory behavior, and their scores were
significantly lower than standard housed offspring of high LG
females (p ? .001). Offspring of both high and low LG females
placed in enriched housing exhibited high levels of exploratory
behavior compared to the standard housed low LG females (p ?
.01) and impoverished housed high and low LG females (p ? .05)
but did not differ from each other or from standard housed off-
spring of high LG females. No group differences were found in
total activity in the open field during the testing session.
One week following open-field testing, females were assessed in
the object-recognition test. Females were videotaped during a
5-min exposure to a new and old object. We conducted an analysis
using a discrimination ratio, a measure of the ratio of time spent
with the new versus the old object. Higher ratios indicate that
relatively more time was spent with the new object. Two-way
ANOVA indicated a main effect of group, F(1, 34) ? 8.4, p ? .01,
and a main effect of housing, F(2, 34) ? 13.4, p ? .001, on the
discrimination ratio. Offspring of high LG mothers exhibited
higher discrimination ratios compared to offspring of low LG
mothers (p ? .05). Females housed in enriched conditions spent
more time investigating the new object compared to standard (p ?
.05) and impoverished (p ? .001) housed females.
OTR Binding of Differentially Housed Offspring of High
and Low LG Mothers
Lactating females (n ? 5 per group) were decapitated on Day 6
postpartum, and their brains were processed for OTR binding
the adult female offspring of high and low LG dams. Offspring were
weaned into three housing conditions (standard, impoverished, or enriched)
for 50 days, mated, and observed during the first 6 days postpartum.
Analysis indicated that postweaning impoverishment and enrichment abol-
ished group differences in maternal LG. High LG female offspring housed
under impoverished conditions exhibited reduced levels of LG compared to
standard housed high LG females (p ? .05), whereas low LG female
offspring housed under enriched conditions exhibited elevated levels of LG
compared to standard housed low LG females (p ? .001). Error bars
represent standard error of the mean.*p ? .05.***p ? .001.
Mean percentage of time spent licking/grooming (LG) pups by
CHAMPAGNE AND MEANEY
assay. The six regions analyzed were the MPOA, bed nucleus of
the stria terminalis (BNST), lateral septum, paraventricular nu-
cleus (PVN), central nucleus of the amygdala, and ventral medial
nucleus of the hypothalamus (VMH). Repeated-measures ANOVA
indicated a main effect of group, F(1, 29) ? 45.3, p ? .001; a main
effect of housing, F(2, 29) ? 65.8, p ? .001; a main effect of
region, F(5, 29) ? 187.7, p ? .001; a significant Group ? Housing
Condition interaction, F(2, 29) ? 5.9, p ? .01; a Group ? Region
interaction, F(5, 29) ? 5.4, p ? .001; a Housing ? Region
interaction, F(10, 29) ? 8.4, p ? .001; and a significant three-way
Group ? Housing Condition ? Region interaction, F(10, 29) ?
2.3, p ? .05.
Results and representative photomicrographs are presented in
Table 1 and Figure 3. In the MPOA, Tukey post hoc analyses
indicated elevated levels of OTR binding in the offspring of high
LG females compared to low LG females weaned into standard
housing conditions (p ? .001). Under impoverished and enriched
housing conditions, there were no significant group differences.
OTR binding in the MPOA of offspring of high LG females
housed in impoverished conditions was significantly lower than
high LG/standard housed females (p ? .01). OTR binding in the
offspring of low LG females housed in enriched conditions was
significantly higher than that of low LG/standard housed females
(p ? .01). In the BNST, standard housed offspring of high LG
females had significantly elevated levels of OTR binding com-
pared to low LG/standard housed females (p ? .05). No group
differences in binding were observed under impoverished condi-
tions. Under enriched conditions, binding in the BNST of high LG
offspring was significantly elevated compared to low LG females
(p ? .05). Binding in both high and low LG female offspring
housed under enriched conditions was elevated compared to low
LG/standard housed females (p ? .001 and p ? .05, respectively).
In the lateral septum, standard housed offspring of high LG dams
had higher OTR binding levels than low LG dams (p ? .05). No
group differences in binding were observed under impoverished or
enriched housing conditions. In the PVN, high/low LG differences
in OTR binding were detected under standard housing conditions
(p ? .05). Under impoverished and enriched housing conditions,
no group differences were observed. Binding in high LG/
impoverished females was not significantly different from binding
in low LG/standard housed females. OTR binding in the PVN of
low LG/enriched females was significantly elevated compared to
that of low LG/standard housed females (p ? .05). In the central
nucleus of the amygdala, OTR binding was significantly elevated
in the offspring of high LG females compared to low LG females
housed in standard conditions (p ? .001). Group differences were
not observed under impoverished or enriched conditions. High
LG/impoverished females had significantly lower levels of OTR
binding than high LG/standard housed females in this region (p ?
.01). Higher levels of binding were detected in low LG/enriched
housed females compared to low LG/standard housed females
(p ? .01). Finally, post hoc analyses of binding in the VMH
indicated no significant differences as a function of group or
Exploration and Activity of Male Offspring of
Differentially Housed Females
From each of the six groups (high and low grand-maternal
phenotypes by three housing conditions) of females, 15 adult male
offspring were tested as adults in the open-field task. Two-way
ANOVA of exploratory behavior (time spent in inner-field) indi-
cated a main effect of group, F(1, 59) ? 45.2, p ? .001; a main
high and low licking/grooming (LG) dams. Under standard postweaning
housing conditions, high LG offspring were more exploratory than low LG
offspring. Analysis indicated that high LG female offspring housed under
impoverished conditions exhibited reduced levels of exploration compared
to standard housed high LG females (p ? .001), whereas low LG female
offspring housed under enriched conditions exhibited elevated levels of
exploration compared to standard housed low LG females (p ? .01). Error
bars represent standard error of the mean.*p ? .05.***p ? .001.
Mean open-field exploration of the adult female offspring of
Mean (SEM) Oxytocin Receptor Binding Levels in Offspring of
Low and High LG Dams as a Function of Postweaning Housing
Postweaning housing condition
hypothalamus; BNST ? bed nucleus of the stria terminalis; LS ? lateral
septum; PVN ? paraventricular nucleus; VMH ? ventral medial nucleus
of the hypothalamus.
*p ? .05.
LG ? licking/grooming; MPOA ? medial preoptic area of the
***p ? .001.
EFFECTS OF ENVIRONMENT ON MATERNAL CARE
effect of housing, F(2, 59) ? 30.7, p ? .001; and a significant
Group ? Housing Condition interaction, F(2, 59) ? 23.0, p ?
.001. Post hoc analysis indicated that the male offspring of high
LG/standard housed females exhibited higher levels of exploration
than the male offspring of low LG/standard housed females (p ?
.001; see Figure 4). The male offspring of females housed in
impoverished and enriched conditions showed no group differ-
ences in exploration. The male offspring of both high LG/
impoverished and low LG/impoverished females showed reduced
exploration compared to the male offspring of high LG/standard
housed females (p ? .001). Male offspring of low LG/enriched
females were significantly more exploratory than offspring of low
LG/standard housed females (p ? .001). No significant differ-
ences were found in overall activity of the male offspring in the
open field as a function of mother’s group or housing condition.
From each of the six conditions, 8 male offspring were tested in
the object-recognition task (see Figure 5). Two-way ANOVA of
the discrimination ratio (time spent exploring new vs. old object)
indicated a main effect of group, F(1, 34) ? 12.5, p ? .001; a main
effect of housing, F(2, 34) ? 13.3, p ? .001; and a significant
Group ? Housing Condition interaction, F(2, 34) ? 9.8, p ? .001.
Post hoc analyses indicated significantly higher discrimination
ratios in the male offspring of high LG/standard housed females
compared to the offspring of low LG/standard housed females
(p ? .001). No group differences were observed in the offspring
of impoverished or enriched females. The offspring of high LG/
impoverished females were significantly less exploratory than
offspring of high LG/standard housed females (p ? .001). No
group differences were observed in overall total time spent explor-
ing objects during the testing session.
Postweaning Housing Effects on the Transgenerational
Inheritance of Maternal Behavior
Female offspring of differentially housed mothers (n ? 14 per
group) were mated and observed with their litters for 6 days
postpartum. Two-way ANOVA of LG scores indicated a main
receptor binding in Day 6 postpartum lactating female offspring of high
and low licking/grooming (LG) dams. Females were placed at weaning into
standard (STD), impoverished (IMPOV), or enriched (ENRICH) housing
conditions. LS ? lateral septum; BNST ? bed nucleus of the stria termi-
nalis; MPOA ? medial preoptic area of the hypothalamus; VMH ? ventral
medial nucleus of the hypothalamus; cAMYG ? central nucleus of the
Representative photomicrographs of hypothalamic-oxytocin
standard, impoverished, or enriched housed females (who were themselves
the offspring of standard housed high and low licking/grooming mothers).
Error bars represent standard error of the mean.***p ? .001.
Mean open-field exploration of the adult male offspring of
object in a 5-min session observed in the adult male offspring of standard,
impoverished, or enriched housed females, who were themselves the
offspring of high and low licking/grooming (LG) mothers. Discrimination
ratios of male offspring of high LG/standard housed females were elevated
compared to the offspring of low LG females (p ? .001). The male
offspring of high LG/impoverished housed females were significantly less
exploratory than offspring of high LG/standard housed females (p ? .001).
Error bars represent standard error of the mean.***p ? .001.
Mean ratio of time spent exploring a novel versus familiar
CHAMPAGNE AND MEANEY
effect of group, F(1, 42) ? 5.8, p ? .05; a main effect of housing,
F(2, 42) ? 29.0, p ? .001; and a significant Group ? Housing
Condition interaction, F(2, 42) ? 4.0, p ? .05 (see Figure 6). Post
hoc analysis indicated that female offspring of high LG/standard
housed females engaged in higher levels of LG than offspring of
low LG/standard housed females (p ? .01). Offspring of high
LG/impoverished females exhibited significantly lower levels of
LG compared to offspring of high LG/standard housed females (p ?
.001). Offspring of low LG/enriched females exhibited higher levels
of LG than low LG/standard housed females (p ? .01).
These results provide evidence for the role of social conditions
beyond the postnatal period in altering patterns of maternal care
and thus offspring phenotype and illustrate the interaction between
the effects of postnatal and postweaning environments. Thus, the
female offspring of dams that provided low levels of LG stimula-
tion toward pups during the 1st week postpartum period, if placed
into socially enriched postweaning conditions, exhibited high lev-
els of LG toward their own pups, and the offspring of high LG
dams placed into social isolation during the postweaning period
exhibited low levels of LG toward their offspring. However,
amongst low LG females placed in social isolation and high LG
females placed in social enrichment there was no change in phe-
notype. Moreover, these altered patterns of maternal care were also
observed in subsequent offspring without manipulation of post-
weaning housing conditions (see Figure 6). Thus there was an
environment-environment interaction through which postnatal and
postweaning social interactions mediated variations in adult ma-
ternal care and shaped the transmission of these variations across
generations (see Figure 7).
The patterns of behavior of these females in response to social
environment are associated with altered levels of OTR binding in
brain regions critical to maternal care (Numan, 1988; Stack, Bal-
akrishnan, Numan, & Numan, 2002), such as the MPOA, and in
those regions associated with indices of anxiety (Davis & Whalen,
2001), such as the PVN and amygdala. Previous studies examining
the reversibility of postnatally induced changes in the neuroendo-
crine system through postweaning social enrichment have indi-
cated that the underlying neural substrates are unaffected despite
the behavioral changes observed (Francis, Diorio, Plotsky, &
Meaney, 2002). However, both the peripheral and central oxytocin
system display an incredible degree of plasticity as a normal
process of the reproductive cycle in response to elevated hormone
levels (Bale & Dorsa, 1997; Breton & Zingg, 1997; De Kloet,
Voorhuis, & Elands, 1985; Montagnese, Poulain, Vincent, &
Theodosis, 1988; Theodosis & Poulain, 1992). Estrogen is a potent
up-regulator of OTR levels, and we have shown that the offspring
of high and low LG mothers differ in estrogen sensitivity, partic-
ularly in the MPOA (Champagne et al., 2001; Champagne,
Weaver, et al., 2003). Thus, in the offspring of low LG dams there
is no dose response increase in OTR binding in the MPOA in
response to increasing doses of estradiol. This lack of response is
thought to be mediated by decreased levels of ER? expression in
the MPOA of the offspring of low compared to high LG dams
(Champagne, Weaver, et al., 2003). It is the decrease in ER?
expression associated with decreased LG received in infancy that
may generate stable individual differences in maternal care and
mediate the transmission of these natural variations in behavior
across generations. These transgenerational effects are associated
with epigenetic regulation of the expression of ER? through dif-
ferential DNA methylation of the promoter region of this gene
during the postnatal period (Champagne et al., 2006). Though it is
possible that epigenetic regulation of steroid receptors may ac-
count for postweaning effects on OTR binding, there are other
mechanisms through which these changes could be achieved (Bale
et al., 2001; Zingg et al., 1998). Previous studies have indicated
that social isolation during the postweaning period results in de-
creased biosynthesis of estradiol and estrone in female rats (Ful-
gheri, Di Prisco, & Verdarelli, 1975). This suppression in estradiol
may reduce increases in OTR binding in the hypothalamus that
occur as females reach sexual maturity (Tribollet, Charpak,
Schmidt, Dubois-Dauphin, & Dreifuss, 1989; Tribollet, Goumaz,
Raggenbass, & Dreifuss, 1991) and prevent estrogen-induced up-
regulation of OTR binding observed in high LG females during
lactation, resulting in a phenotype that resembles that of a low LG
dam. It is perhaps this plasticity in oxytocin neurons and receptors
in response to environmental and hormonal cues that allows for the
dynamic regulation of maternal care by the environment.
The effects of postnatal social isolation on maternal behavior
that we have observed are consistent with those previously re-
ported in both primates (Harlow et al., 1965; Ruppenthal, Arling,
Harlow, Sackett, & Suomi, 1976) and rodents (Brunelli, Shindle-
decker, & Hofer, 1989; Gonzalez, Lovic, Ward, Wainwright, &
Fleming, 2001; Lovic et al., 2001). In Harlow’s artificial rearing
studies, female infant rhesus macaques displayed impairments in
maternal behavior as adults, engaging in high levels of abuse and
neglect (Arling & Harlow, 1967; Harlow & Suomi, 1971; Seay,
Alexander, & Harlow, 1964). Females exposed to social restriction
rather than total deprivation spent less time in contact with their
infants and were observed to nurse less frequently (Schapiro,
Bloomsmith, Suarez, & Porter, 1995). In rodents, artificially reared
the adult female offspring of standard, impoverished, or enriched housed
females (who were themselves the offspring of high and low LG dams).
Female offspring of high LG/standard housed females were higher in LG
than offspring of low LG/standard housed females (p ? .01). Offspring of
high LG/impoverished females exhibited significantly lower levels of LG
compared to offspring of high LG/standard housed females (p ? .001).
Offspring of low LG/enriched females exhibited higher levels of LG than
low LG/standard housed females (p ? .01). Error bars represent standard
error of the mean.**p ? .01.
Mean percentage of time spent licking/grooming (LG) pups by
EFFECTS OF ENVIRONMENT ON MATERNAL CARE
females displayed deficits in maternal LG and contact toward their
own pups (Fleming et al., 2002). Artificial rearing under social
conditions (in which pups are raised with one peer) can ameliorate
the deficits normally observed and produce females who provide
adequate levels of maternal care (Gonzalez et al., 2001). The
partial isolation of pups, using the maternal separation paradigm,
has also been found to exert long-term consequences for maternal
behavior (Boccia & Pedersen, 2001; Fleming et al., 2002; Ladd et
al., 2000; Liu et al., 2000; Plotsky & Meaney, 1993; Pryce,
Bettschen, & Feldon, 2001), with females showing deficits in
maternal LG toward their own offspring (Fleming et al., 2002).
Taken together, these studies have illustrated the developmental
impact of social contact, particularly between mother and infant. In
humans, these effects are also evident. Infants raised in institu-
tional settings have elevated cortisol levels and are at high risk for
developmental disorders (Carlson & Earls, 1997; MacLean, 2003).
Children who are raised in environments characterized by neglect
show impairments in learning and memory, a heightened response
to stress, and an increased risk of psychopathology (Briere &
Runtz, 1988; Egeland, Sroufe, & Erickson, 1983; Trickett &
McBride-Chang, 1995). Social contact appears to play an impor-
tant role in regulating stress reactivity. In rats, examples of socially
facilitated behavior (Clayton, 1978) include reduction in fearful-
ness (Davitz & Mason, 1955; Epley, 1974) and increased explor-
atory behavior (Simmel, 1962). In preadolescent rats, presence of
familiar conspecifics reduces novelty-induced corticosterone lev-
els (Terranova, Cirulli, & Laviola, 1999). Our findings of in-
creased exploratory behavior and reduced behavioral indices of
anxiety in females exposed to social enrichment during the juve-
nile period are consistent with this earlier work.
One of the issues addressed by the current study and previous
work with postweaning environmental manipulation (Bredy,
Humpartzoomian, Cain, & Meaney, 2003; Francis et al., 2002) is
that of reversibility, i.e., can the effects of early environment be
altered later in the course of development? Despite the severity of
the impairments resulting from maternal separation and social
isolation described in primates and rodents, there is evidence that
reversal is possible through social stimulation. Socially isolated
rhesus monkeys, placed into continuous contact with peers, began
to show normal social interaction (Harlow et al., 1965). Likewise,
females who were isolation reared and showed deficits in maternal
behavior began to show more species-typical mother–infant inter-
actions following prolonged contact with infants (Harlow &
Suomi, 1971). Females could thus “recover,” showing low levels
of abuse and neglect toward subsequent offspring. The deficits in
maternal behavior shown by socially restricted rhesus monkeys
could also be overcome, either by allowing for social interaction
with peers or, to some degree, by allowing females to observe
mother–infant interactions of socially housed rhesus females
(Schapiro et al., 1995). Thus, behavioral patterns that can be
predicted from experiences occurring early in development can be
altered through subsequent environmental conditions.
Plasticity in both maternal care and central OTRs in response to
postnatal and postweaning environmental cues provides a potential
the transmission of maternal behavior across generations. In the grand-maternal generation (F0), all females are
housed under standard postweaning conditions. Offspring of these high and low licking/grooming (LG) females
(F1) are then weaned into three housing conditions that differ in the levels of social interaction provided. All F1
females placed into social isolation were observed to be low LG, and all F1females placed into enriched social
housing were observed to be high LG, regardless of the characteristics of the maternal phenotype of F0. Under
standard housing conditions, F1maternal phenotype is the same as F0maternal phenotype. Grand-offspring (F2)
are all housed under standard postweaning conditions and share the same LG phenotype as F1.
Summary of research design and results indicating the effects of postweaning social conditions on
CHAMPAGNE AND MEANEY
mechanism through which offspring phenotype can be adapted to
the environmental conditions into which they will be reared. Under
stressful conditions, such as those experienced during social iso-
lation, decreases in maternal LG result in reduced exploratory
behavior and decreased LG of offspring, consistent with previous
studies in which gestational stress decreased maternal LG and
central levels of OTR, with similar effects on subsequent genera-
tions (Champagne & Meaney, 2006). From an evolutionary per-
spective, these disruptive conditions would predict a highly vari-
able environment in which a heightened behavioral response to
stressful situations would allow an individual to respond more
rapidly to environmental change and increase likelihood of sur-
vival. By altering the quality of mother–infant interactions, these
adaptive behavioral responses can then be passed on to subsequent
The social environment experienced during development has a
significant role in regulating adult maternal care and exploratory
behavior. Our findings suggest that though mother–infant interac-
tions during the postnatal period typically predict the adult phe-
notype of offspring, social environment experienced beyond this
period can alter the predicted phenotype. Thus, offspring that have
received reduced levels of care during the postnatal period and are
thus predicted to be more inhibited of novelty and provide less care
to their own offspring can “recover” in response to juvenile social
enrichment. Likewise, juvenile social isolation can reduce explo-
ration of a novel environment and decrease maternal care in those
females who would be predicted to be exploratory and show high
levels of maternal care toward their offspring based on the high
level of care they received during the postnatal period. Our results
suggest that environmental change occurring later in development
can induce phenotypic changes in an organism, which interact with
effects mediated by cues obtained from earlier periods of devel-
opment, in this case providing an example of an environment-
environment interaction. This developmental plasticity may pro-
duce an adult phenotype that is optimally suited to the
environmental conditions of adulthood. The long-term effects of
social experiences during the postnatal and postweaning period on
maternal behavior create a mechanism through which traits can be
“inherited” by subsequent generations (Gluckman, Hanson, Spen-
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Received January 24, 2007
Revision received July 16, 2007
Accepted July 23, 2007 ?
Correction to St. Andre and Reilly (2007)
In the article “Effects of Central and Basolateral Amygdala Lesions on Conditioned Taste Aversion
and Latent Inhibition,” by Justin St. Andre and Steve Reilly (Behavioral Neuroscience, 2007, Vol.
121, No. 1, pp. 90–99), Figure 4 on p. 96 (Results and Discussion, Experiment 2: Behavioral
section) was incorrect. The correct figure is printed below.
N-methyl-D-aspartate lesions of the basolateral amygdala (BLAX) during the preexposure and conditioning
phases of Experiment 2.
Mean (? SE) saccharin intake for the nonlesion (SHAM) control rats and for rats with bilateral
EFFECTS OF ENVIRONMENT ON MATERNAL CARE
Correction to Champagne and Meaney (2007)
In the article “Transgenerational Effects of Social Environment on Variations in Maternal Care and
Behavioral Response to Novelty,” by Frances A. Champagne and Michael J. Meaney (Behavioral
Neuroscience, 2007, Vol. 121, No. 6, pp. 1353–1363), Figure 1 on Page 1356 was incorrect. The
correct figure is printed below.
low LG dams. Offspring were weaned into three housing conditions (standard, impoverished, or enriched) for
50 days, mated, and observed during the first 6 days postpartum. Analysis indicated that posweaning impov-
erishment and enrichment abolished group differences in maternal LG. High LG female offspring housed under
impoverished conditions exhibited reduced levels of LG compared to standard housed high LG females
(p ? .05), whereas low LG female offspring housed under enriched conditions exhibited elevated levels of LG
compared to standard housed low LG females (p ? .001). Error bars represent standard error of the mean
*p ? .05.***p ? .001.
Mean percentage of time spent licking/grooming (LG) pups by the adult female offspring of high and