Nov 18, 2008

Chronic reductions in serotonin transporter function prevent 5-HT1B-induced behavioral effects in mice

Biological Psychiatry
Nancy A ShanahanStephanie C Dulawa

Abstract

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, images, or impulses and/or repetitive stereotypical behavior. Obsessive-compulsive disorder patients exhibit reduced prepulse inhibition (PPI) and symptom exacerbation after challenge with 5-HT1B receptor agonists. Recently, gain-of-function alleles of the serotonin transporter (5-HTT) have been associated with OCD. We tested the hypothesis that reducing 5-HTT function chronically, either genetically or via serotonin reuptake inhibitor (SRI) treatment, attenuates PPI deficits and perseverative hyperlocomotion induced by 5-HT1B agonists in mice. Mice received subchronic or chronic pretreatment with the SRI fluoxetine and acute treatment with RU24969 (5-HT1A/1B agonist) or 8-OH-DPAT (5-HT1A agonist) and were assessed for PPI, locomotor activity, and spatial patterns of locomotion. The same measures were evaluated in 5-HTT wild-type (WT), heterozygous (HT), and knockout (KO) mice after RU24969 treatment. The effects of WAY100635 (5-HTA antagonist) or GR127935 (5-HT1B/D antagonist) pretreatment on RU24969-induced effects were evaluated. Finally, 5-HT1B binding and functional coupling were assessed in 5-HTT-WT, -HT, and -KO mice, and normal fluoxetine-treate...Continue Reading

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Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Pyridines
Serotonin Reuptake Inhibitor [EPC]
Exertion
Neurologic Manifestations
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Globus Pallidus
Mice, Inbred BALB C
C57BL/6 Mouse
Piperazines

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