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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 repeated restraint stress and social isolation during preadolescence on depression-related behaviors in adult drd3-EGFP mice.Adult male (A and B) and female (C and D) drd3-EGFP mice were either not stressed (blue, n = 7) or subjected to repeated restraint stress during preadolescence (red, n = 7). Latency to immobility (A and C) and total immobility time (B and D) were measured in the Porsolt Forced Swim test. Significant reduction in latency to immobility and increase in total immobility time were observed in adult male and female drd3-EGFP mice that were subjected to repeated restraint stress during preadolescence (*, p<0.001). Error bars represents ± SEM.
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pone.0143908.g006: Effect of repeated restraint stress and social isolation during preadolescence on depression-related behaviors in adult drd3-EGFP mice.Adult male (A and B) and female (C and D) drd3-EGFP mice were either not stressed (blue, n = 7) or subjected to repeated restraint stress during preadolescence (red, n = 7). Latency to immobility (A and C) and total immobility time (B and D) were measured in the Porsolt Forced Swim test. Significant reduction in latency to immobility and increase in total immobility time were observed in adult male and female drd3-EGFP mice that were subjected to repeated restraint stress during preadolescence (*, p<0.001). Error bars represents ± SEM.

Mentions: In adulthood, male drd3-EGFP mice that were subjected to preadolescence repetitive restraint stress and social isolation exhibited decreased latency to immobility (p<0.001, U = 8.5, Mann-Whitney Rank Sum test; Fig 6A) and increased total immobility time (p<0.001, U = 12.5, Mann-Whitney Rank Sum test; Fig 6B), in the Porsolt Forced Swim test, compared to non-stressed littermates. In the Porsolt Forced Swim test, reduction in latency to immobility and increased total immobility time, result from behavioral despair which is an endophenotype of depression-related behaviors in animal models. Interestingly, in contrast to the male-specific effect on anxiety shown in Figs 1 and 2, the preadolescent stress-induced changes in latency to immobility and total immobility (p = 0.004, U = 3.0, Mann-Whitney Rank Sum test and p = 0.003, Student’s t-test, respectively) were also observed in adult female drd3-EGFP mice subjected to the preadolescent restraint stress and social isolation treatment (Fig 6C and 6D). Together these results suggest that repetitive restraint stress during preadolescence and social isolation results in the development of depression-related behaviors in adulthood, in both male and female mice.


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

Seo JH, Kuzhikandathil EV - PLoS ONE (2015)

Effect of repeated restraint stress and social isolation during preadolescence on depression-related behaviors in adult drd3-EGFP mice.Adult male (A and B) and female (C and D) drd3-EGFP mice were either not stressed (blue, n = 7) or subjected to repeated restraint stress during preadolescence (red, n = 7). Latency to immobility (A and C) and total immobility time (B and D) were measured in the Porsolt Forced Swim test. Significant reduction in latency to immobility and increase in total immobility time were observed in adult male and female drd3-EGFP mice that were subjected to repeated restraint stress during preadolescence (*, p<0.001). Error bars represents ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664486&req=5

pone.0143908.g006: Effect of repeated restraint stress and social isolation during preadolescence on depression-related behaviors in adult drd3-EGFP mice.Adult male (A and B) and female (C and D) drd3-EGFP mice were either not stressed (blue, n = 7) or subjected to repeated restraint stress during preadolescence (red, n = 7). Latency to immobility (A and C) and total immobility time (B and D) were measured in the Porsolt Forced Swim test. Significant reduction in latency to immobility and increase in total immobility time were observed in adult male and female drd3-EGFP mice that were subjected to repeated restraint stress during preadolescence (*, p<0.001). Error bars represents ± SEM.
Mentions: In adulthood, male drd3-EGFP mice that were subjected to preadolescence repetitive restraint stress and social isolation exhibited decreased latency to immobility (p<0.001, U = 8.5, Mann-Whitney Rank Sum test; Fig 6A) and increased total immobility time (p<0.001, U = 12.5, Mann-Whitney Rank Sum test; Fig 6B), in the Porsolt Forced Swim test, compared to non-stressed littermates. In the Porsolt Forced Swim test, reduction in latency to immobility and increased total immobility time, result from behavioral despair which is an endophenotype of depression-related behaviors in animal models. Interestingly, in contrast to the male-specific effect on anxiety shown in Figs 1 and 2, the preadolescent stress-induced changes in latency to immobility and total immobility (p = 0.004, U = 3.0, Mann-Whitney Rank Sum test and p = 0.003, Student’s t-test, respectively) were also observed in adult female drd3-EGFP mice subjected to the preadolescent restraint stress and social isolation treatment (Fig 6C and 6D). Together these results suggest that repetitive restraint stress during preadolescence and social isolation results in the development of depression-related behaviors in adulthood, in both male and female mice.

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