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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

Histological analysis of intra-NAc fluosphere injection sites (a) and the region of plPFC that comprised the largest density of retrogradely-traced neurons, and was therefore analyzed (b). Numerals indicate mm from bregma. The largest (solid) and smallest (shaded) bolus sizes of all animals included in analysis are indicated. All injection sites were within ±10% in size.
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brainsci-03-00143-f006: Histological analysis of intra-NAc fluosphere injection sites (a) and the region of plPFC that comprised the largest density of retrogradely-traced neurons, and was therefore analyzed (b). Numerals indicate mm from bregma. The largest (solid) and smallest (shaded) bolus sizes of all animals included in analysis are indicated. All injection sites were within ±10% in size.

Mentions: In order to define the discrete region of plPFC where projections to the NAc reside, retrograde tracer was injected into the NAc core [18]. Rats were anesthetized with a ketamine/xylazine mixture and a Hamilton syringe was stereotaxically lowered into the NAc core. Coordinates for juveniles were AP: +2.1, ML: +1.3, DV: −6.5 and coordinates for adolescents were AP: +1.8, ML: +1.2, DV: −6.8 [64]. Coordinates for adults were AP: +1.6; ML: +1.2, DV: −6.8 [66]. One micrometer of 660λ fluospheres (Molecular Probes) was injected over 2 min, after which the needle remained in the brain for an additional minute to ensure diffusion into the surrounding tissue, based on our previous methodology [18]. Fluospheres were used because fibers of passage are not affected such that only direct projections are stained [67]. Fluosphere bolus spread and intensity was measured using Leica confocal software (Leica Microsystems, Heidelberg, Germany) to verify that a consistent amount of tracer was introduced into all animals, as previously reported ([18]; Figure 6).


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

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

Histological analysis of intra-NAc fluosphere injection sites (a) and the region of plPFC that comprised the largest density of retrogradely-traced neurons, and was therefore analyzed (b). Numerals indicate mm from bregma. The largest (solid) and smallest (shaded) bolus sizes of all animals included in analysis are indicated. All injection sites were within ±10% in size.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

brainsci-03-00143-f006: Histological analysis of intra-NAc fluosphere injection sites (a) and the region of plPFC that comprised the largest density of retrogradely-traced neurons, and was therefore analyzed (b). Numerals indicate mm from bregma. The largest (solid) and smallest (shaded) bolus sizes of all animals included in analysis are indicated. All injection sites were within ±10% in size.
Mentions: In order to define the discrete region of plPFC where projections to the NAc reside, retrograde tracer was injected into the NAc core [18]. Rats were anesthetized with a ketamine/xylazine mixture and a Hamilton syringe was stereotaxically lowered into the NAc core. Coordinates for juveniles were AP: +2.1, ML: +1.3, DV: −6.5 and coordinates for adolescents were AP: +1.8, ML: +1.2, DV: −6.8 [64]. Coordinates for adults were AP: +1.6; ML: +1.2, DV: −6.8 [66]. One micrometer of 660λ fluospheres (Molecular Probes) was injected over 2 min, after which the needle remained in the brain for an additional minute to ensure diffusion into the surrounding tissue, based on our previous methodology [18]. Fluospheres were used because fibers of passage are not affected such that only direct projections are stained [67]. Fluosphere bolus spread and intensity was measured using Leica confocal software (Leica Microsystems, Heidelberg, Germany) to verify that a consistent amount of tracer was introduced into all animals, as previously reported ([18]; Figure 6).

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