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Early life adversity alters the developmental profiles of addiction-related prefrontal cortex circuitry.

Brenhouse HC, Lukkes JL, Andersen SL - Brain Sci (2013)

Bottom Line: Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC).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).Our findings reveal microcircuitry-specific changes caused by early life adversity that could help explain heightened vulnerability to drug addiction during adolescence.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA. h.brenhouse@neu.edu.

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.

No MeSH data available.


Related in: MedlinePlus

Density of traced cells per mm2 in the plPFC of CON (white bars) and MS (black bars) rats at three ages. * p < 0.05 difference from juveniles within the same stress group. Averages ± SEM are presented.
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brainsci-03-00143-f004: Density of traced cells per mm2 in the plPFC of CON (white bars) and MS (black bars) rats at three ages. * p < 0.05 difference from juveniles within the same stress group. Averages ± SEM are presented.

Mentions: Consistent with our previous report [18], plPFC projections to the NAc core increased with age (see Figure 4; main effect of Age: F(2,17) = 5.212; p = 0.017). There was no Age × Stress Group interaction (p = 0.182), nor a main effect of Stress Group (main effect of Stress Group: p = 0.248).


Early life adversity alters the developmental profiles of addiction-related prefrontal cortex circuitry.

Brenhouse HC, Lukkes JL, Andersen SL - Brain Sci (2013)

Density of traced cells per mm2 in the plPFC of CON (white bars) and MS (black bars) rats at three ages. * p < 0.05 difference from juveniles within the same stress group. Averages ± SEM are presented.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061828&req=5

brainsci-03-00143-f004: Density of traced cells per mm2 in the plPFC of CON (white bars) and MS (black bars) rats at three ages. * p < 0.05 difference from juveniles within the same stress group. Averages ± SEM are presented.
Mentions: Consistent with our previous report [18], plPFC projections to the NAc core increased with age (see Figure 4; main effect of Age: F(2,17) = 5.212; p = 0.017). There was no Age × Stress Group interaction (p = 0.182), nor a main effect of Stress Group (main effect of Stress Group: p = 0.248).

Bottom Line: Drug addiction typically manifests during adolescence in parallel with the later-developing prefrontal cortex (PFC).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).Our findings reveal microcircuitry-specific changes caused by early life adversity that could help explain heightened vulnerability to drug addiction during adolescence.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA. h.brenhouse@neu.edu.

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.

No MeSH data available.


Related in: MedlinePlus