Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis
Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. So...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-01-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2013.00223/full |
| _version_ | 1811339156811415552 |
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| author | Gian David Greenberg Gian David Greenberg Abigail eLaman-Maharg Abigail eLaman-Maharg Katharine L Campi Heather eVoigt Veronica N Orr Leslie eSchaal Brian Charles Trainor Brian Charles Trainor |
| author_facet | Gian David Greenberg Gian David Greenberg Abigail eLaman-Maharg Abigail eLaman-Maharg Katharine L Campi Heather eVoigt Veronica N Orr Leslie eSchaal Brian Charles Trainor Brian Charles Trainor |
| author_sort | Gian David Greenberg |
| collection | DOAJ |
| description | Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females. |
| first_indexed | 2024-04-13T18:22:01Z |
| format | Article |
| id | doaj.art-d48f2ce8d2914c11b03d6cd09726fc48 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-04-13T18:22:01Z |
| publishDate | 2014-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-d48f2ce8d2914c11b03d6cd09726fc482022-12-22T02:35:25ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532014-01-01710.3389/fnbeh.2013.0022373395Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalisGian David Greenberg0Gian David Greenberg1Abigail eLaman-Maharg2Abigail eLaman-Maharg3Katharine L Campi4Heather eVoigt5Veronica N Orr6Leslie eSchaal7Brian Charles Trainor8Brian Charles Trainor9University of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisUniversity of California, DavisDepression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus), a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF) protein but not mRNA in the bed nucleus of the stria terminalis (BNST) in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc). The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB) antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.http://journal.frontiersin.org/Journal/10.3389/fnbeh.2013.00223/fullBDNFSexSocial DefeatDoseSSRIBNST |
| spellingShingle | Gian David Greenberg Gian David Greenberg Abigail eLaman-Maharg Abigail eLaman-Maharg Katharine L Campi Heather eVoigt Veronica N Orr Leslie eSchaal Brian Charles Trainor Brian Charles Trainor Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis Frontiers in Behavioral Neuroscience BDNF Sex Social Defeat Dose SSRI BNST |
| title | Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis |
| title_full | Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis |
| title_fullStr | Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis |
| title_full_unstemmed | Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis |
| title_short | Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis |
| title_sort | title sex differences in stress induced social withdrawal role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis |
| topic | BDNF Sex Social Defeat Dose SSRI BNST |
| url | http://journal.frontiersin.org/Journal/10.3389/fnbeh.2013.00223/full |
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