title: Blockade of 5-HT(2) receptors in the periaqueductal grey matter (PAG) abolishes the anxiolytic-like effect of 5-HT(1A) receptor antagonism in the median raphe nucleus in mice.
abstract: 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-HT(1A) 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-HT(1A) or 5-HT(2) 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-HT(2) receptors within the PAG. Mice received combined intra-PAG injection with ketanserin (10 nmol/0.1 μl), a 5-HT(2) receptor antagonist, followed by intra-MRN injection of WAY-100635 (5.6 nmol/0.1 μl), a highly selective 5-HT(1A) 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.
authors.affiliation: Psychobiology Group/Department of Psychology/CECH-UFSCar, São Carlos, SP, 13565-905, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nunes-de-Souza
authors.forename: Ricardo
authors.initials: R
authors.lastname: Nunes-de-Souza
authors.forename: Robert John
authors.initials: RJ
authors.lastname: Rodgers
authors.forename: Azair
authors.initials: A
authors.lastname: Canto-de-Souza
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008845:Microinjections / Q000523:psychology; D010487:Periaqueductal Gray / Q000187:drug effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D011903:Raphe Nuclei / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D014151:Anti-Anxiety Agents; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D007650:Ketanserin