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Lasting neurobehavioral abnormalities in rats after neonatal activation of serotonin 1A and 1B receptors: possible mechanisms for serotonin dysfunction in autistic spectrum disorders
- Source :
- Psychopharmacology. 231:1191-1200
- Publication Year :
- 2013
- Publisher :
- Springer Science and Business Media LLC, 2013.
-
Abstract
- Perinatal exposure of rats to selective serotonin reuptake inhibitors (SSRIs) produces sensory and social abnormalities paralleling those seen in autistic spectrum disorders (ASDs). However, the possible mechanism(s) by which this exposure produces behavioral abnormalities is unclear. We hypothesized that the lasting effects of neonatal SSRI exposure are a consequence of abnormal stimulation of 5-HT1A and/or 5-HT1B receptors during brain development. We examined whether such stimulation would result in lasting sensory and social deficits in rats in a manner similar to SSRIs using both direct agonist stimulation of receptors as well as selective antagonism of these receptors during SSRI exposure. Male and female rat pups were treated from postnatal days 8 to 21. In Experiment 1, pups received citalopram (20 mg/kg/day), saline, (±)-8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT; 0.5 mg/kg/day) or 7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]-quinoxaline dimaleate (CGS-12066B; 10 mg/kg/day). In Experiment 2, a separate cohort of pups received citalopram (20 mg/kg/day), or saline which was combined with either N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclo-hexanecarboxamide maleate (WAY-100635; 0.6 mg/kg/day) or N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1-1′-biphenyl-4-carboxamide (GR-127935; 6 mg/kg/day) or vehicle. Rats were then tested in paradigms designed to assess sensory and social response behaviors at different time points during development. Direct and indirect neonatal stimulation of 5-HT1A or 5-HT1B receptors disrupts sensory processing, produces neophobia, increases stereotypic activity, and impairs social interactions in manner analogous to that observed in ASD. Increased stimulation of 5-HT1A and 5-HT1B receptors plays a significant role in the production of lasting social and sensory deficits in adult animals exposed as neonates to SSRIs.
- Subjects :
- Male
Agonist
medicine.medical_specialty
Pyridines
medicine.drug_class
Stimulation
Citalopram
Pharmacology
Article
Piperazines
chemistry.chemical_compound
Quinoxalines
Internal medicine
medicine
Animals
Rats, Long-Evans
Freezing Reaction, Cataleptic
Social Behavior
Receptor
GR-127935
8-Hydroxy-2-(di-n-propylamino)tetralin
Oxadiazoles
8-OH-DPAT
Brain
Rats
Serotonin Receptor Agonists
Endocrinology
Animals, Newborn
chemistry
Receptor, Serotonin, 5-HT1A
Exploratory Behavior
Receptor, Serotonin, 5-HT1B
Antidepressant
Female
Serotonin Antagonists
Serotonin
Psychology
Locomotion
Selective Serotonin Reuptake Inhibitors
medicine.drug
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 231
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....9d72289d513a4a8e5669524b1656cbb2