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Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry
Department of Psychology, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA
McLean Hospital, 115 Mill St, Belmont, MA 02478, USA
* Author to whom correspondence should be addressed.
Received: 25 October 2012; in revised form: 11 December 2012 / Accepted: 24 January 2013 / Published: 4 February 2013
Abstract: Early adverse experience is a well-known risk factor for addictive behaviors later in life. Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC). While it has been shown that dopaminergic modulation within the PFC is involved in addiction-like behaviors, little is known about how early adversity modulates its development. Here, we report that maternal separation stress (4 h per day between postnatal days 2–20) alters the development of the prelimbic PFC. Immunofluorescence and confocal microscopy revealed differences between maternally-separated and control rats in dopamine D1 and D2 receptor expression during adolescence, and specifically the expression of these receptors on projection neurons. In control animals, D1 and D2 receptors were transiently increased on all glutamatergic projection neurons, as well as specifically on PFC→nucleus accumbens projection neurons (identified with retrograde tracer). Maternal separation exacerbated the adolescent peak in D1 expression and blunted the adolescent peak in D2 expression on projection neurons overall. However, neurons retrogradely traced from the accumbens expressed lower levels of D1 during adolescence after maternal separation, compared to controls. Our findings reveal microcircuitry-specific changes caused by early life adversity that could help explain heightened vulnerability to drug addiction during adolescence.
Keywords: maternal separation; prefrontal cortex; dopamine receptors; nucleus accumbens
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Brenhouse, H.C.; Lukkes, J.L.; Andersen, S.L. Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry. Brain Sci. 2013, 3, 143-158.
Brenhouse HC, Lukkes JL, Andersen SL. Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry. Brain Sciences. 2013; 3(1):143-158.
Brenhouse, Heather C.; Lukkes, Jodi L.; Andersen, Susan L. 2013. "Early Life Adversity Alters the Developmental Profiles of Addiction-Related Prefrontal Cortex Circuitry." Brain Sci. 3, no. 1: 143-158.