Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice
Background. Selective serotonin reuptake inhibitor (SSRI) therapy complicates up to 10% of pregnancies. During therapy, SSRIs exert pleiotropic antidepressant, anorexigenic, and neurotrophic effects. Intrauterine SSRI exposure has been modeled by neonatal administration to developmentally immature r...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | Journal of Nutrition and Metabolism |
| Online Access: | http://dx.doi.org/10.1155/2012/431574 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850176878427504640 |
|---|---|
| author | Gary J. Kummet Sarah E. Haskell Gregory M. Hermann Charles Ni Kenneth A. Volk Areej K. Younes Alise K. Miller Robert D. Roghair |
| author_facet | Gary J. Kummet Sarah E. Haskell Gregory M. Hermann Charles Ni Kenneth A. Volk Areej K. Younes Alise K. Miller Robert D. Roghair |
| author_sort | Gary J. Kummet |
| collection | DOAJ |
| description | Background. Selective serotonin reuptake inhibitor (SSRI) therapy complicates up to 10% of pregnancies. During therapy, SSRIs exert pleiotropic antidepressant, anorexigenic, and neurotrophic effects. Intrauterine SSRI exposure has been modeled by neonatal administration to developmentally immature rodents, and it has paradoxically elicited features of adult depression. We hypothesized neonatal SSRI exposure likewise programs a rebound hypermetabolic state in adult mice. Methods. C57BL/6 pups were randomized to saline or sertraline (5 mg/kg/d) from P1–P14. Because estrogen increases tryptophan hydroxylase 2 (TPH2) expression, a subset of female mice underwent sham surgery or bilateral ovariectomy (OVX). Metabolic rate was determined by indirect calorimetry. Results. In both male and female mice, neonatal SSRI exposure increased adult caloric intake and metabolic rate. SSRI-exposed female mice had significantly decreased adult weight with a relative increase in brain weight and melatonin excretion, independent of ovarian status. Cerebral cortex TPH2 expression was increased in SSRI-exposed male mice but decreased in OVX SSRI-exposed female mice. Conclusions. SSRI exposure during a critical neurodevelopmental window increases adult caloric intake and metabolic rate. Ovarian status modulated central TPH2 expression, but not adult energy balance, suggesting programmed neural connectivity or enhanced melatonin production may play a more important role in the post-SSRI hypermetabolic syndrome. |
| format | Article |
| id | doaj-art-b836b851ddfc4d8ebb71794e771e81aa |
| institution | OA Journals |
| issn | 2090-0724 2090-0732 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Nutrition and Metabolism |
| spelling | doaj-art-b836b851ddfc4d8ebb71794e771e81aa2025-08-20T02:19:10ZengWileyJournal of Nutrition and Metabolism2090-07242090-07322012-01-01201210.1155/2012/431574431574Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult MiceGary J. Kummet0Sarah E. Haskell1Gregory M. Hermann2Charles Ni3Kenneth A. Volk4Areej K. Younes5Alise K. Miller6Robert D. Roghair7Department of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADepartment of Pediatrics, Carver College of Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USABackground. Selective serotonin reuptake inhibitor (SSRI) therapy complicates up to 10% of pregnancies. During therapy, SSRIs exert pleiotropic antidepressant, anorexigenic, and neurotrophic effects. Intrauterine SSRI exposure has been modeled by neonatal administration to developmentally immature rodents, and it has paradoxically elicited features of adult depression. We hypothesized neonatal SSRI exposure likewise programs a rebound hypermetabolic state in adult mice. Methods. C57BL/6 pups were randomized to saline or sertraline (5 mg/kg/d) from P1–P14. Because estrogen increases tryptophan hydroxylase 2 (TPH2) expression, a subset of female mice underwent sham surgery or bilateral ovariectomy (OVX). Metabolic rate was determined by indirect calorimetry. Results. In both male and female mice, neonatal SSRI exposure increased adult caloric intake and metabolic rate. SSRI-exposed female mice had significantly decreased adult weight with a relative increase in brain weight and melatonin excretion, independent of ovarian status. Cerebral cortex TPH2 expression was increased in SSRI-exposed male mice but decreased in OVX SSRI-exposed female mice. Conclusions. SSRI exposure during a critical neurodevelopmental window increases adult caloric intake and metabolic rate. Ovarian status modulated central TPH2 expression, but not adult energy balance, suggesting programmed neural connectivity or enhanced melatonin production may play a more important role in the post-SSRI hypermetabolic syndrome.http://dx.doi.org/10.1155/2012/431574 |
| spellingShingle | Gary J. Kummet Sarah E. Haskell Gregory M. Hermann Charles Ni Kenneth A. Volk Areej K. Younes Alise K. Miller Robert D. Roghair Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice Journal of Nutrition and Metabolism |
| title | Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice |
| title_full | Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice |
| title_fullStr | Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice |
| title_full_unstemmed | Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice |
| title_short | Neonatal SSRI Exposure Programs a Hypermetabolic State in Adult Mice |
| title_sort | neonatal ssri exposure programs a hypermetabolic state in adult mice |
| url | http://dx.doi.org/10.1155/2012/431574 |
| work_keys_str_mv | AT garyjkummet neonatalssriexposureprogramsahypermetabolicstateinadultmice AT sarahehaskell neonatalssriexposureprogramsahypermetabolicstateinadultmice AT gregorymhermann neonatalssriexposureprogramsahypermetabolicstateinadultmice AT charlesni neonatalssriexposureprogramsahypermetabolicstateinadultmice AT kennethavolk neonatalssriexposureprogramsahypermetabolicstateinadultmice AT areejkyounes neonatalssriexposureprogramsahypermetabolicstateinadultmice AT alisekmiller neonatalssriexposureprogramsahypermetabolicstateinadultmice AT robertdroghair neonatalssriexposureprogramsahypermetabolicstateinadultmice |