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Dopamine D3 Receptor Mediates Preadolescent Stress-Induced Adult Psychiatric Disorders.

Seo JH, Kuzhikandathil EV - PLoS ONE (2015)

Bottom Line: We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood.In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus.Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Physiology and Neurosciences, Rutgers-New Jersey Medical School, Newark, NJ, 07103, United States of America.

ABSTRACT
Several studies have shown that repeated stressful experiences during childhood increases the likelihood of developing depression- and anxiety-related disorders in adulthood; however, the underlying mechanisms are not well understood. We subjected drd3-EGFP and drd3- mice to daily, two hour restraint stress episodes over a five day period during preadolescence (postnatal day 35 to 39), followed by social isolation. When these mice reached adulthood (post-natal day > 90), we assessed locomotor behavior in a novel environment, and assessed depression-related behavior in the Porsolt Forced Swim test. We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood. Adult male mice subjected to restraint stress during preadolescence exhibited both anxiety- and depression-related behaviors; however, adult female mice subjected to preadolescent restraint stress exhibited only depression-related behaviors. The development of preadolescent stress-derived psychiatric disorders was blocked by D3 receptor selective antagonist, SB 277011-A, and absent in D3 receptor mice. Adult male mice that experienced stress during preadolescence exhibited a loss of D3 receptor expression and function in the amygdala but not in hippocampus or nucleus accumbens. In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus. Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood.

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Effect of D3 receptor genetic ablation on preadolescent stress-induced depression-related behaviors in adult mice.Male (A and B) and female (C and D) drd3- mice, in adulthood, did not show significant difference in latency to immobility (A and C) and total immobility time (B and D) regardless of whether they were subjected preadolescent repeated restraint stress and social isolation. N = 6 animals. Error bars represents ± SEM.
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pone.0143908.g007: Effect of D3 receptor genetic ablation on preadolescent stress-induced depression-related behaviors in adult mice.Male (A and B) and female (C and D) drd3- mice, in adulthood, did not show significant difference in latency to immobility (A and C) and total immobility time (B and D) regardless of whether they were subjected preadolescent repeated restraint stress and social isolation. N = 6 animals. Error bars represents ± SEM.

Mentions: To determine the role of dopamine D3 receptor in preadolescent stress-induced adult depression-related disorders, we subjected male and female drd3 mice to the preadolescent restraint stress and social isolation protocol and assessed depression-related behaviors in adulthood. In adulthood, male drd3- mice that were subjected to preadolescence repetitive restraint stress and social isolation exhibited no significant difference in latency to immobility (p = 0.31, Student’s t-test; Fig 7A) and total immobility time (p = 0.69, U = 10, Mann-Whitney Rank Sum test; Fig 7B), in the Porsolt Forced Swim test, compared to non-stressed littermates. Similarly, adult female drd3- mice subjected to the preadolescent restraint stress and social isolation treatment exhibited no significant difference in latency to immobility (p = 0.663, Student’s t-test; Fig 7C) and total immobility time (p = 0.421, U = 8.5, Mann-Whitney Rank Sum test; Fig 7D), in the Porsolt Forced Swim test, compared to non-stressed littermates.


Dopamine D3 Receptor Mediates Preadolescent Stress-Induced Adult Psychiatric Disorders.

Seo JH, Kuzhikandathil EV - PLoS ONE (2015)

Effect of D3 receptor genetic ablation on preadolescent stress-induced depression-related behaviors in adult mice.Male (A and B) and female (C and D) drd3- mice, in adulthood, did not show significant difference in latency to immobility (A and C) and total immobility time (B and D) regardless of whether they were subjected preadolescent repeated restraint stress and social isolation. N = 6 animals. Error bars represents ± SEM.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664486&req=5

pone.0143908.g007: Effect of D3 receptor genetic ablation on preadolescent stress-induced depression-related behaviors in adult mice.Male (A and B) and female (C and D) drd3- mice, in adulthood, did not show significant difference in latency to immobility (A and C) and total immobility time (B and D) regardless of whether they were subjected preadolescent repeated restraint stress and social isolation. N = 6 animals. Error bars represents ± SEM.
Mentions: To determine the role of dopamine D3 receptor in preadolescent stress-induced adult depression-related disorders, we subjected male and female drd3 mice to the preadolescent restraint stress and social isolation protocol and assessed depression-related behaviors in adulthood. In adulthood, male drd3- mice that were subjected to preadolescence repetitive restraint stress and social isolation exhibited no significant difference in latency to immobility (p = 0.31, Student’s t-test; Fig 7A) and total immobility time (p = 0.69, U = 10, Mann-Whitney Rank Sum test; Fig 7B), in the Porsolt Forced Swim test, compared to non-stressed littermates. Similarly, adult female drd3- mice subjected to the preadolescent restraint stress and social isolation treatment exhibited no significant difference in latency to immobility (p = 0.663, Student’s t-test; Fig 7C) and total immobility time (p = 0.421, U = 8.5, Mann-Whitney Rank Sum test; Fig 7D), in the Porsolt Forced Swim test, compared to non-stressed littermates.

Bottom Line: We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood.In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus.Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, Physiology and Neurosciences, Rutgers-New Jersey Medical School, Newark, NJ, 07103, United States of America.

ABSTRACT
Several studies have shown that repeated stressful experiences during childhood increases the likelihood of developing depression- and anxiety-related disorders in adulthood; however, the underlying mechanisms are not well understood. We subjected drd3-EGFP and drd3- mice to daily, two hour restraint stress episodes over a five day period during preadolescence (postnatal day 35 to 39), followed by social isolation. When these mice reached adulthood (post-natal day > 90), we assessed locomotor behavior in a novel environment, and assessed depression-related behavior in the Porsolt Forced Swim test. We also measured the expression and function of dopamine D3 receptor in limbic brain areas such as hippocampus, nucleus accumbens and amygdala in control and stressed drd3-EGFP mice in adulthood. Adult male mice subjected to restraint stress during preadolescence exhibited both anxiety- and depression-related behaviors; however, adult female mice subjected to preadolescent restraint stress exhibited only depression-related behaviors. The development of preadolescent stress-derived psychiatric disorders was blocked by D3 receptor selective antagonist, SB 277011-A, and absent in D3 receptor mice. Adult male mice that experienced stress during preadolescence exhibited a loss of D3 receptor expression and function in the amygdala but not in hippocampus or nucleus accumbens. In contrast, adult female mice that experienced preadolescent stress exhibited increased D3 receptor expression in the nucleus accumbens but not in amygdala or hippocampus. Our results suggest that the dopamine D3 receptor is centrally involved in the etiology of adult anxiety- and depression-related behaviors that arise from repeated stressful experiences during childhood.

Show MeSH
Related in: MedlinePlus