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Queen's University
 

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Research: Developmental Neurobiology

Early life experiences have a profound impact on both behavioural and biological development.  For example, children who live in abusive or neglectful environments exhibit altered physiological responses to stress when they are adults, and have an increased likelihood of developing psychiatric disorders including addiction.

For more information on specific projects related to this topic:

Early Adverse Experience and Drug Addiction

Kim Hellemans studied the relationship between adverse early experience and  the propensity to develop drug addiction by examining behavioural traits of rats reared in social isolation.  Initially, we confirmed that rats reared in social isolation show increased anxiety, greater emotional reactivity to an acutely painful event, and an impairment on learning to escape from an aversive environment (water). Interestingly, animals who were removed from isolation at adolescence and placed in enriched environments performed normally on all tests.  Manipulating the early environment of rats also produced dramatic brain changes. Whereas rats raised in complex social environments have larger brains and more densely packed neurons in the outer cortex, isolation-reared rats had thinner cortices indicating a reduced number of neurons in this brain region. Switching the rats from isolation to enrichment partially reversed this neural change. Subsequent work demonstrated that isolation rearing has no effect on motor impulsivity, but decreases cognitive impulsivity. Our characterization of neural changes following differential rearing suggested that altered serotonergic function may underlie these behavioural differences. In a related line of work, we collaborated with James Reynolds (Dept. of Molecular and Biomedical Sciences) to show that alcohol exposure in utero increases impulsive behaviours and the propensity to self-administer drugs in adolescence.  This animal model of fetal alcohol syndrome provides another means to examine the effect of early adverse experience on the development of drug addiction.

Publications:

Shea, A.J, Hewitt, A.M., Olmstead, M.C., Brien, J.F., & Reynolds, J.M. (2011). Moderate ethanol consumption by the pregnant guinea pig produces neurobeahvioural deficits and increases ethanol preference in offspring. Behavioural Pharmacology, (in press).

Olmstead, M.C., Martin, A., Brien, J.F. & Reynolds, J.N. (2009). Chronic prenatal ethanol exposure increases disinhibition and perseverative responding in the adult guinea pig. Behavioural Pharmacology, 20, 554-557.

Hayward, M.L., Martin, A.E., Brien, J.F., Dringenberg, H.C., Olmstead, M.C. & Reynolds, J.N. (2004).  Chronic prenatal ethanol exposure impairs conditioned responding and enhances GABA release in the hippocampus of the adult guinea pig. Journal of Pharmacology and Experimental Therapeutics, 308, 644-650.

Hellemans, K.G.C., Nobrega, J.N. & Olmstead, M.C. (2005). E arly environmental experience alters baseline and ethanol-induced cognitive impulsivity: Relationship to forebrain 5-HT1A receptor binding. Behavioural Brain Research, 159, 207-220.



Hellemans, K.G.C., Benge, L.C. & Olmstead, M.C. (2004). Adolescent enrichment partially reverses the social isolation syndrome. Developmental Brain Research, 150, 103-115.

Adolescent Vulnerability to Addictive Disorders

Mammalian species (including humans) exhibit increased impulsivity, risk-taking and sensation-seeking during adolescence, changes that are associated with maturation of the prefrontal cortex.  Not surprisingly, adolescence is also the age at which most humans experiment with abused drugs and/or develop eating disorders.  Animal models of binge eating disorder have suggested the importance of two synergistic factors in the development of this disorder: a history of restriction-refeeding cycles (i.e., “yo-yo dieting”) and anxiety-generating events. One problem with these models is that they do not explain why some people who diet and undergo stress do not develop binge eating disorder. Stephanie Hancock investigated individual differences in the etiology of binge eating disorder by examining how early life experiences alter responses to stress and dieting. One of the most reliable predictors of stress responses in adulthood is the level of maternal care that a pup receives in early life. In collaboration with Janet Menard we measured maternal behaviour towards pups during the first week after birth, and then subjected offspring to repeated cycles of “yo-yo dieting” and/or footshock stress, beginning either in adolescence or adulthood. When the stressful events were initiated in adolescence, females displayed stress-induced binge, only if they received low levels of maternal care after birth (i.e., low licking/grooming). A history of dieting exacerbated the effect, but was ineffective on its own. Binge eating did not occur in offspring of mothers who exhibited high levels of maternal care, or in any animal that experienced stress and dieting in adulthood. These data suggest that low levels of maternal care in early life increase the vulnerability to stress-induced binge eating, and that this heightened vulnerability is manifested during the adolescent period.

Publications:

Hancock, S.D., & Olmstead, M.C.  (2010). Animal models of eating disorders. In: Olmstead, M.C. (Ed.).  Animal Models of Drug Addiction Totowa NJ: Humana Press Inc.

Hancock, S.D., Menard, J.L. & Olmstead, M.C. (2005). Variations in maternal care influence vulnerability to stress-induced binge eating in female rats. Physiology and Behavior, 85, 430-439.

Stress in Childhood Predicts Depression and Anxiety

In humans, early life adversity is a strong predictor of anxiety and depression in adulthood.  Some evidence suggests that the nature of adverse experience (e.g., childhood neglect versus abuse) predisposes individuals to develop a particular symptoms of these disorders.  Joanna Pohl tested this hypothesis in animal models by exposing young male and female rats to environmental conditions modeling abuse or neglect, and testing them as adults in a variety of behavioural tests. In males, severe sporadic stress only altered anxiety-related responses whereas, in females, severe sporadic stress altered both anxiety- and depression-related responses.  Overall, females appeared more sensitive than males to the impact of childhood-adolescent stress and exhibited a broader spectrum of outcomes, including changes in both anxiety- and depression-like responses.  Our findings reiterate the importance of early life experience on the development of adult psychopathologies and emphasize the need to consider both gender and experience effects in these analyses. This work is an on-going collaboration with Janet Menard, Kate Harkness and Kathy Wynne-Edwards.

Publications:



Pohl, J.L., Olmstead, M.C., Wynne-Edwards, K.E., Harkness, K.L. & Menard, J.L. (2007). Repeated exposure to stress across the peripubertal-juvenile period alters rats’ anxiety- and depression-like behaviors in adulthood: The importance of stressor type and gender. Behavioral Neuroscience, 121, 462-474.

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