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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 number of center zone entries in an open field arena by adult drd3- mice.Adult male (A, and B) and female (C and D) drd3- mice were either not stressed (blue, n = 5) or subjected to repeated restraint stress and social isolation during preadolescence (red, n = 5). Number of center zone entries were measured in an Open Field test in adulthood. Significant increase in number of entries was observed in stressed male drd3- mice during the initial 10 minute period following the placement of the mice in the arena (*, p<0.05, two-way repeated measure ANOVA, post-hoc SNK test; A). The total number of center zone entries over the entire 60 minute observation period was also significantly increase in stressed male drd3- mice (*, p<0.05, Student’s t-test). The stress-induced changes in locomotor activity was absent in adult female drd3- mice subjected to preadolescent stress and social isolation (C and D). Error bars represents ± SEM.
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pone.0143908.g004: Effect of repeated restraint stress and social isolation during preadolescence on number of center zone entries in an open field arena by adult drd3- mice.Adult male (A, and B) and female (C and D) drd3- mice were either not stressed (blue, n = 5) or subjected to repeated restraint stress and social isolation during preadolescence (red, n = 5). Number of center zone entries were measured in an Open Field test in adulthood. Significant increase in number of entries was observed in stressed male drd3- mice during the initial 10 minute period following the placement of the mice in the arena (*, p<0.05, two-way repeated measure ANOVA, post-hoc SNK test; A). The total number of center zone entries over the entire 60 minute observation period was also significantly increase in stressed male drd3- mice (*, p<0.05, Student’s t-test). The stress-induced changes in locomotor activity was absent in adult female drd3- mice subjected to preadolescent stress and social isolation (C and D). Error bars represents ± SEM.

Mentions: Male drd3- mice that were subjected to preadolescent repetitive restraint stress followed by social isolation exhibited, in adulthood, a significant increase in number of center zone entries in a novel arena (p = 0.026, F1,88 = 7.458, two-way repeated measure ANOVA; Fig 4A) wherein, post-hoc SNK test revealed significant difference between the non-stressed and stressed mice only at the 5 min (q = 4.077, p = 0.006) and 10 min (q = 3.428, p = 0.02) time points. The large increase in center zone entries during the 5 to 10 min interval resulted in an overall increase in center zone entries over the entire 60 minute monitoring period (p = 0.026, Student’s t-test; Fig 4B). Female drd3- mice that were subjected to preadolescent repetitive restraint stress followed by social isolation did not exhibit, in adulthood, a significant change in number of center zone entries in a novel environment (p = 0.376, F1,88 = 0.877, two-way repeated measure ANOVA; Fig 4C) and, post-hoc SNK test did not reveal significant difference between the non-stressed and stressed mice at any time points. There was also no significant difference in number of center zone entries during the entire 60 minute monitoring period (p = 0.376, Student’s t-test; Fig 4D).


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 number of center zone entries in an open field arena by adult drd3- mice.Adult male (A, and B) and female (C and D) drd3- mice were either not stressed (blue, n = 5) or subjected to repeated restraint stress and social isolation during preadolescence (red, n = 5). Number of center zone entries were measured in an Open Field test in adulthood. Significant increase in number of entries was observed in stressed male drd3- mice during the initial 10 minute period following the placement of the mice in the arena (*, p<0.05, two-way repeated measure ANOVA, post-hoc SNK test; A). The total number of center zone entries over the entire 60 minute observation period was also significantly increase in stressed male drd3- mice (*, p<0.05, Student’s t-test). The stress-induced changes in locomotor activity was absent in adult female drd3- mice subjected to preadolescent stress and social isolation (C and D). Error bars represents ± SEM.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664486&req=5

pone.0143908.g004: Effect of repeated restraint stress and social isolation during preadolescence on number of center zone entries in an open field arena by adult drd3- mice.Adult male (A, and B) and female (C and D) drd3- mice were either not stressed (blue, n = 5) or subjected to repeated restraint stress and social isolation during preadolescence (red, n = 5). Number of center zone entries were measured in an Open Field test in adulthood. Significant increase in number of entries was observed in stressed male drd3- mice during the initial 10 minute period following the placement of the mice in the arena (*, p<0.05, two-way repeated measure ANOVA, post-hoc SNK test; A). The total number of center zone entries over the entire 60 minute observation period was also significantly increase in stressed male drd3- mice (*, p<0.05, Student’s t-test). The stress-induced changes in locomotor activity was absent in adult female drd3- mice subjected to preadolescent stress and social isolation (C and D). Error bars represents ± SEM.
Mentions: Male drd3- mice that were subjected to preadolescent repetitive restraint stress followed by social isolation exhibited, in adulthood, a significant increase in number of center zone entries in a novel arena (p = 0.026, F1,88 = 7.458, two-way repeated measure ANOVA; Fig 4A) wherein, post-hoc SNK test revealed significant difference between the non-stressed and stressed mice only at the 5 min (q = 4.077, p = 0.006) and 10 min (q = 3.428, p = 0.02) time points. The large increase in center zone entries during the 5 to 10 min interval resulted in an overall increase in center zone entries over the entire 60 minute monitoring period (p = 0.026, Student’s t-test; Fig 4B). Female drd3- mice that were subjected to preadolescent repetitive restraint stress followed by social isolation did not exhibit, in adulthood, a significant change in number of center zone entries in a novel environment (p = 0.376, F1,88 = 0.877, two-way repeated measure ANOVA; Fig 4C) and, post-hoc SNK test did not reveal significant difference between the non-stressed and stressed mice at any time points. There was also no significant difference in number of center zone entries during the entire 60 minute monitoring period (p = 0.376, Student’s t-test; Fig 4D).

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