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- Blockade of 5-HT2 receptors in the periaqueductal grey matter (PAG) abolishes the anxiolytic-like effect of 5-HT1A receptor antagonism in the median raphe nucleus in mice
- Universidade Estadual Paulista (UNESP)
- Universidade Federal de São Carlos (UFSCar)
- Universidade de São Paulo (USP)
- Univ Leeds
- Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
- Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
- CNPq: 303580/2009-7
- Several lines of evidence support the involvement of serotonergic (5-HT) neurons of the median raphe nucleus (MRN) in anxiety-like behaviour. In this context, it is known that blockade of 5-HT1A somatodendritic autoreceptors in the midbrain raphe nuclei increases the firing rate of these neurons, disinhibiting 5-HT release in postsynaptic target areas such as amygdala, hippocampus and periaqueductal grey matter (PAG). However, while activation of 5-HT1A or 5-HT2 receptors in forebrain targets such as the amygdala or hippocampus enhances anxiety-like behaviours in rodents, stimulation of both receptor subtypes in the midbrain PAG markedly reduces anxiety-like behaviour. In view of these findings, the present study investigated whether the anti-anxiety effects induced by pharmacological disinhibition of 5-HT neurons in the MRN are attenuated by the blockade of 5-HT2 receptors within the PAG. Mice received combined intra-PAG injection with ketanserin (10 nmol/0.1 mu l), a 5-HT2 receptor antagonist, followed by intra-MRN injection of WAY-100635 (5.6 nmol/0.1 mu l), a highly selective 5-HT1A receptor antagonist. They were then individually exposed to the elevated plus-maze (EPM), with the videotaped behavioural sessions subsequently scored for both conventional and ethological measures. The results confirmed that intra-MRN infusion of WAY100635 reduces behavioural indices of anxiety without significantly altering general activity measures, and further showed that this effect was completely blocked by intra-PAG pretreatment with an intrinsically-inactive dose of ketanserin. Together, these results suggest that 5HT(2) receptor populations located within the midbrain PAG play a significant role in the reduction of anxiety observed following disinhibition of 5-HT neurons in the MRN. (C) 2011 Published by Elsevier B.V.
- Behavioural Brain Research. Amsterdam: Elsevier B.V., v. 225, n. 2, p. 547-553, 2011.
- Elsevier B.V.
- Elevated plus-maze
- 5-HT2 receptors
- Median raphe nucleus
- Acesso restrito
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