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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

Peak D1R (a) and D2R (b) expression on PFC→NAc projections in adolescence is absent after MS. * p < 0.05 difference between stress groups using Bonferroni post-hoc t-tests after 2-way ANOVA. @ p < 0.05 difference from juveniles. White bars: CON; Black bars: MS. Averages ± SEM are presented. Representative photomicrographs from CON adolescent animals displaying receptor-ir, retrograde tracer, and colocalization (arrows) are shown in (c). Bar: 20 µm. Images cropped and enlarged for clarity. n = 6 for all treatment groups.
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brainsci-03-00143-f005: Peak D1R (a) and D2R (b) expression on PFC→NAc projections in adolescence is absent after MS. * p < 0.05 difference between stress groups using Bonferroni post-hoc t-tests after 2-way ANOVA. @ p < 0.05 difference from juveniles. White bars: CON; Black bars: MS. Averages ± SEM are presented. Representative photomicrographs from CON adolescent animals displaying receptor-ir, retrograde tracer, and colocalization (arrows) are shown in (c). Bar: 20 µm. Images cropped and enlarged for clarity. n = 6 for all treatment groups.

Mentions: A focused study of projection neurons bound for the NAc specifically revealed important distinctions in how MS affects plPFC microcircuitry. Confocal analysis of traced neurons co-expressing D1R and D2R revealed an interaction between group and age for both D1R and D2R. Notably, while MS was found to exacerbate the adolescent increase of D1R on all glutamatergic neurons, the peak of D1R on plPFC→NAc neurons was decreased by 27% in MS adolescents compared to CON adolescents (Age × Stress Group interaction: F(2,22) = 6.4; p = 0.006; Figure 5a). Post-hoc comparisons revealed that this interaction was driven by differences between MS and CON adolescents (t(9) = 2.27; p = 0.05). While D1R was differentially affected on plPFC→NAc neurons compared to the overall population of glutamate neurons, MS had consistent effects on D2R across all projection neurons, with MS adolescents displaying fewer D2R on plPFC→NAc neurons during adolescence compared to CON (Age × Stress Group interaction: F(2,22) = 8.1; p = 0.002; Figure 5b). Post-hoc analyses of D2R-ir traced neurons revealed that MS adolescents displayed significantly less D2R expression on plPFC→NAc cells than CON adolescents (t(9) = 3.79; p = 0.004). In other words, traced neurons in CON adolescents expressed significantly more D1R and D2R than juveniles and adults (p < 0.05 for both receptors), but MS adolescents did not display a similar peak for either receptor.


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

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

Peak D1R (a) and D2R (b) expression on PFC→NAc projections in adolescence is absent after MS. * p < 0.05 difference between stress groups using Bonferroni post-hoc t-tests after 2-way ANOVA. @ p < 0.05 difference from juveniles. White bars: CON; Black bars: MS. Averages ± SEM are presented. Representative photomicrographs from CON adolescent animals displaying receptor-ir, retrograde tracer, and colocalization (arrows) are shown in (c). Bar: 20 µm. Images cropped and enlarged for clarity. n = 6 for all treatment groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

brainsci-03-00143-f005: Peak D1R (a) and D2R (b) expression on PFC→NAc projections in adolescence is absent after MS. * p < 0.05 difference between stress groups using Bonferroni post-hoc t-tests after 2-way ANOVA. @ p < 0.05 difference from juveniles. White bars: CON; Black bars: MS. Averages ± SEM are presented. Representative photomicrographs from CON adolescent animals displaying receptor-ir, retrograde tracer, and colocalization (arrows) are shown in (c). Bar: 20 µm. Images cropped and enlarged for clarity. n = 6 for all treatment groups.
Mentions: A focused study of projection neurons bound for the NAc specifically revealed important distinctions in how MS affects plPFC microcircuitry. Confocal analysis of traced neurons co-expressing D1R and D2R revealed an interaction between group and age for both D1R and D2R. Notably, while MS was found to exacerbate the adolescent increase of D1R on all glutamatergic neurons, the peak of D1R on plPFC→NAc neurons was decreased by 27% in MS adolescents compared to CON adolescents (Age × Stress Group interaction: F(2,22) = 6.4; p = 0.006; Figure 5a). Post-hoc comparisons revealed that this interaction was driven by differences between MS and CON adolescents (t(9) = 2.27; p = 0.05). While D1R was differentially affected on plPFC→NAc neurons compared to the overall population of glutamate neurons, MS had consistent effects on D2R across all projection neurons, with MS adolescents displaying fewer D2R on plPFC→NAc neurons during adolescence compared to CON (Age × Stress Group interaction: F(2,22) = 8.1; p = 0.002; Figure 5b). Post-hoc analyses of D2R-ir traced neurons revealed that MS adolescents displayed significantly less D2R expression on plPFC→NAc cells than CON adolescents (t(9) = 3.79; p = 0.004). In other words, traced neurons in CON adolescents expressed significantly more D1R and D2R than juveniles and adults (p < 0.05 for both receptors), but MS adolescents did not display a similar peak for either receptor.

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