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5-HT<inf>2A</inf> receptors are involved in cognitive but not antidepressant effects of fluoxetine

AuthorsCastañé, Anna ; Kargieman, Lucila ; Celada, Pau ; Bortolozzi, Analía ; Artigas, Francesc
Keywords5-HT2A receptors
Antidepressant drugs
Prefrontal cortex
Novel object recognition
Tail suspension test
Working memory
Issue Date1-Aug-2015
PublisherEuropean College of Neuropsychopharmacology
CitationEuropean Neuropsychopharmacology 25(8): 1353-1361 (2015)
Abstract© 2015 Elsevier B.V. and ECNP. The prefrontal cortex (PFC) plays a crucial role in cognitive and affective functions. It contains a rich serotonergic (serotonin, 5-HT) innervation and a high density of 5-HT receptors. Endogenous 5-HT exerts robust actions on the activity of pyramidal neurons in medial PFC (mPFC) via excitatory 5-HT<inf>2A</inf> and inhibitory 5-HT<inf>1A</inf> receptors, suggesting the involvement of 5-HT neurotransmission in cortical functions. However, the underlying mechanisms must be elucidated. Here we examine the role of 5-HT<inf>2A</inf> receptors in the processing of emotional and cognitive signals evoked by increasing the 5-HT tone after acute blockade of the 5-HT transporter. Fluoxetine (5-20mg/kg i.p.) dose-dependently reduced the immobility time in the tail-suspension test in wild-type (WT) and 5-HT<inf>2A</inf> knockout (KO2A) mice, with non-significant differences between genotypes. Fluoxetine (10mg/kg i.p.) significantly impaired mice performance in the novel object recognition test 24h post-administration in WT, but not in KO2A mice. The comparable effect of fluoxetine on extracellular 5-HT in the mPFC of both genotypes suggests that presynaptic differences are not accountable. In contrast, single unit recordings of mPFC putative pyramidal neurons showed that fluoxetine (1.8-7.2mg/kg i.v.) significantly increased neuronal discharge in KO2A but not in WT mice. This effect is possibly mediated by an altered excitatory/inhibitory balance in the PFC in KO2A mice. Overall, the present results suggest that 5-HT<inf>2A</inf> receptors play a detrimental role in long-term memory deficits mediated by an excess 5-HT in PFC.
Publisher version (URL)http://dx.doi.org/10.1016/j.euroneuro.2015.04.006
Identifiersdoi: 10.1016/j.euroneuro.2015.04.006
issn: 1873-7862
Appears in Collections:(IIBB) Artículos
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