Food &
Function
PAPER
Cite this: Food Funct., 2017, 8, 2592
Received 15th March 2017,
Accepted 30th June 2017
DOI: 10.1039/c7fo00408g
rsc.li/food-function
Early maternal separation induces preference for
sucrose and aspartame associated with increased
blood glucose and hyperactivity
L. Aya-Ramos,
a
C. Contreras-Vargas,
a
J. L. Rico
b
and Z. Dueñas *
a
Early life stress and exposure to sweeteners lead to physiological and behavioral alterations in adulthood.
Nevertheless, many genetic and environmental factors as well as the neurobiological mechanisms that
contribute to the development of these disorders are not fully understood. Similarly, evidence about
the long-term metabolic effects of exposure to sweeteners in early life is limited and inconsistent.
This study used an animal model of maternal separation during breastfeeding (MS) to analyze the
effects of early life stress on consumption of sweeteners, weight gain, blood glucose and locomotion.
Rats were housed under a reversed light/dark cycle (lights off at 7:00 h) with ad libitum access to
water and food. In the MS protocol, MS pups were separated from the dam for 6 h per day in two
periods of 180 minutes (7:00–10:00 and 13:00–16:00 h) during the dark phase of postnatal day
(PND) 1 to PND 21. Non-separated (NS) pups served as controls. On PND 22 rats were grouped by sex
and treatment. From PND 26 to PND 50 sucrose and aspartame were provided to rats, and
sweetener intake, body weight and blood glucose-related measures were scored. On PND 50, both
male and female rats were exposed to the open field test to obtain locomotion and anxiety-related
measures. Results showed that both early maternal separation and sweetener intake during adoles-
cence resulted in increased blood glucose and hyperactivity in male rats but not in female rats.
Data suggest that the combination of early stress and exposure to sucrose and aspartame could be a
risk factor for the development of chronic diseases such as diabetes, as well as for behavioral
alterations.
Introduction
Neonatal maternal separation of laboratory animals is an
animal model of stressful experiences such as maternal
neglect or abuse in early life.
1,2
Patients who have eating dis-
orders and dysfunctional hypothalamic–pituitary–adrenal axes
(HPA) are commonly found to have been abused during child-
hood.
3,4
It has also been shown that an adverse environment
in early life is linked to greater susceptibility to development
of various adult diseases including mental disorders, diabetes
and obesity.
5
In fact, experimental studies in rodents have
shown that the presence of the dam during lactation is crucial
for avoiding negative effects on neurological development of
pups.
6
On the other hand, being overweight or obese has also been
linked to psychiatric disorders such as depression and
anxiety,
9
and the prevalence of these conditions has been
increasing worldwide.
7
Obesity has been strongly linked to the
development of metabolic syndrome which is defined as a set
of risk factors for cardiovascular disease and type 2 diabetes
mellitus that includes hypertension, dyslipidemia, increased
fasting glucose and central obesity.
8
Although there is no
single factor responsible for the significant increases in over-
weight and obesity that have emerged over the last decades,
current evidence suggests that the consumption of sucrose
and aspartame is part of this problem.
10
It is also known that
availability and use of caloric sugar substitutes has increased
and that consumers have been led to believe that these pro-
ducts are healthier.
11
However, epidemiological data from
various cohorts show that the use of caloric sweeteners con-
tributes to development of type 2 diabetes mellitus, coronary
heart disease and strokes.
12
Many studies have indicated a strong correlation between
maternal separation and other traumatic events during early
life on the development of behavioral and neuroendocrine
a
Universidad Nacional de Colombia, Bogotá, Facultad de Medicina, Departamento
de Ciencias fisiológicas, Grupo neurobiología y comportamiento, Bogotá,
D.C. 11001, Colombia. E-mail: zjduenasg@unal.edu.co
b
Fundación Universitaria Konrad Lorenz, Facultad de Psicología, Bogotá, D.C.,
Colombia
2592 | Food Funct. , 2017, 8, 2592–2600 This journal is © The Royal Society of Chemistry 2017
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