Effects of chronic fluoxetine treatment on serotonin 1B receptor-induced deficits in delayed alternation
| Autor: | Emily V. Ho, Stephanie C. Dulawa, Stephanie J. Klenotich, Nancy S. Woehrle, Naseem Jamnia |
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| Rok vydání: | 2012 |
| Předmět: |
Elementary cognitive task
medicine.medical_specialty Obsessive-Compulsive Disorder Time Factors behavioral disciplines and activities Spatial memory Mice Internal medicine Fluoxetine Task Performance and Analysis Medicine Animals Receptor Maze Learning Serotonin transporter Pharmacology Delayed alternation biology Dose-Response Relationship Drug business.industry Serotonin 5-HT1 Receptor Agonists Frontal Lobe Mice Inbred C57BL Endocrinology Memory Short-Term biology.protein Receptor Serotonin 5-HT1B Orbitofrontal cortex Female Serotonin business Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Psychopharmacology. 227(3) |
| ISSN: | 1432-2072 |
| Popis: | Obsessive-compulsive disorder (OCD) patients show overactivation of the orbitofrontal cortex and deficits in cognitive tasks that require proper orbitofrontal functioning including delayed alternation tests of spatial working memory. We recently showed that OCD-like behavior is induced in mice by activating orbitofrontal serotonin 1B receptors (5-HT1Bs). However, the role of 5-HT1Bs in delayed alternation remains unclear.We examined the effects of 5-HT1B receptor activation on delayed alternation task (DAT) performance. We also assessed the ability of an effective OCD treatment, fluoxetine, to prevent 5-HT1B-induced deficits in DAT performance.Mice were tested on the DAT after acute treatment with saline, 3 or 6 mg/kg RU24969 (5-HT1B/1A agonist), 0.3 or 3 mg/kg 8-OH-DPAT (5-HT1A agonist), or co-injection with 3 mg/kg RU24969 and 5 mg/kg GR127935 (5-HT1B/1D antagonist). Separate mice were pretreated chronically (28 days) with 10 mg/kg fluoxetine and then tested on the DAT after acute treatment with 3 mg/kg RU24969, 0.3 mg/kg 8-OH-DPAT, or saline.Both doses of RU24969 decreased accuracy and increased latency on the DAT, and GR127935 blocked RU24969-induced effects on accuracy. The 0.3 mg/kg 8-OH-DPAT did not affect the DAT performance, whereas 3 mg/kg increased omissions on the DAT. Finally, RU24969-induced DAT deficits were absent in fluoxetine-pretreated mice.We show that 5-HT1B receptor activation disrupts DAT performance in mice, and chronic fluoxetine pretreatment blocks these 5-HT1B-induced deficits. Our findings suggest that 5-HT1B receptors play an important role in modulating orbitofrontal-dependent delayed alternation. Moreover, 5-HT1B-induced DAT deficits may provide a mouse model for DAT deficits in OCD. |
| Databáze: | OpenAIRE |
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