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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

D1R (a,c) and D2R (b,d) expression changes on CamKIIa-IR glutamatergic neurons after MS in the plPFC. * p < 0.05 difference between 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. n = 5–6. Representative photomicrographs of individual channels and overlays from control adolescents taken at 40× are shown in (c) and (d). Red-outlined white arrows point to CamKIIa neurons, green-outlined white arrows point to D1R (c) or D2R (d) neurons, and yellow pointers point to co-localized neurons. Scale bar: 20 µm.
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brainsci-03-00143-f003: D1R (a,c) and D2R (b,d) expression changes on CamKIIa-IR glutamatergic neurons after MS in the plPFC. * p < 0.05 difference between 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. n = 5–6. Representative photomicrographs of individual channels and overlays from control adolescents taken at 40× are shown in (c) and (d). Red-outlined white arrows point to CamKIIa neurons, green-outlined white arrows point to D1R (c) or D2R (d) neurons, and yellow pointers point to co-localized neurons. Scale bar: 20 µm.

Mentions: As expected, the adolescent peak of D1R (main effect of Age: F(2,24) = 32.01; p < 0.0001) and D2R (main effect of Age: F(2,24) =29.83; p = 0.003) was found to occur on these projection neurons (Figure 3). However, MS disrupted the normal developmental trajectory of DA receptor expression on plPFC glutamatergic neurons. Animals subjected to MS displayed a 79% higher peak of D1R in adolescence compared to CON (Age × Stress Group interaction: F(2,24) = 4.64; p = 0.02; Figure 3a). Post-hoc comparisons revealed more D1R + CamKIIa neurons in MS adolescents compared to CON adolescents (t(10) = −2.37; p = 0.039). In contrast, adolescent rats subjected to MS displayed a 60% reduction in expression of D2R on plPFC projection neurons compared to their CON counterparts (Age × Stress Group interaction: F(2,24) = 4.78; p = 0.018; Figure 3b). Post-hoc analysis of D2R + CamKIIa showed lower colocalized neurons in MS adolescents compared to CON adolescents (t(10) = 2.38; p = 0.04). Effects of MS on D2R endured into adulthood, as MS adults also displayed lower D2R expression on CamKIIa-IR cells (t(8) = 5.75; p < 0.001).


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

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

D1R (a,c) and D2R (b,d) expression changes on CamKIIa-IR glutamatergic neurons after MS in the plPFC. * p < 0.05 difference between 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. n = 5–6. Representative photomicrographs of individual channels and overlays from control adolescents taken at 40× are shown in (c) and (d). Red-outlined white arrows point to CamKIIa neurons, green-outlined white arrows point to D1R (c) or D2R (d) neurons, and yellow pointers point to co-localized neurons. Scale bar: 20 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

brainsci-03-00143-f003: D1R (a,c) and D2R (b,d) expression changes on CamKIIa-IR glutamatergic neurons after MS in the plPFC. * p < 0.05 difference between 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. n = 5–6. Representative photomicrographs of individual channels and overlays from control adolescents taken at 40× are shown in (c) and (d). Red-outlined white arrows point to CamKIIa neurons, green-outlined white arrows point to D1R (c) or D2R (d) neurons, and yellow pointers point to co-localized neurons. Scale bar: 20 µm.
Mentions: As expected, the adolescent peak of D1R (main effect of Age: F(2,24) = 32.01; p < 0.0001) and D2R (main effect of Age: F(2,24) =29.83; p = 0.003) was found to occur on these projection neurons (Figure 3). However, MS disrupted the normal developmental trajectory of DA receptor expression on plPFC glutamatergic neurons. Animals subjected to MS displayed a 79% higher peak of D1R in adolescence compared to CON (Age × Stress Group interaction: F(2,24) = 4.64; p = 0.02; Figure 3a). Post-hoc comparisons revealed more D1R + CamKIIa neurons in MS adolescents compared to CON adolescents (t(10) = −2.37; p = 0.039). In contrast, adolescent rats subjected to MS displayed a 60% reduction in expression of D2R on plPFC projection neurons compared to their CON counterparts (Age × Stress Group interaction: F(2,24) = 4.78; p = 0.018; Figure 3b). Post-hoc analysis of D2R + CamKIIa showed lower colocalized neurons in MS adolescents compared to CON adolescents (t(10) = 2.38; p = 0.04). Effects of MS on D2R endured into adulthood, as MS adults also displayed lower D2R expression on CamKIIa-IR cells (t(8) = 5.75; p < 0.001).

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