Papel de los receptores 5-ht6 en procesos cognitivos y trastornos neuropsiquiátricosmecanismos implicados

Abstract

titulo: Papel de los receptores 5-ht6 en procesos cognitivos y trastornos neuropsiquiatricos: mecanismos implicados resumen: The involvement of the cholinergic system in learning and memory together with the cognitive enhancing propertnes of 5-ht6 receptor antagonists, led us to study the relationship between 5-ht6 receptors and cholinergic neurotransmission. we confirm that 5-ht6 receptor blockade induces hyperactivity of the cholinergic system. a selective cholinergic lesión of the nbm failed to alter 5-ht6 receptor expression in the deafferentated frontal cortex of wistar rats, suggesting that 5-HT6 receptors are not "located on cholinergic neurons. Respect to the cognitive-enhancing properties of 5-HT6 receptors, subchronic treatment with sb-271046, a selective 5-ht6 antagonist, improved acquisition in the Morris water maze. MK-801 induced learning impairments and a behavioural syndrome that was reversed by sb-271046. Combined treatment with galanthamine and sb-271046 reversed the scopolamine- or MK-801-induced learning impairments. Moreover, training in the MWM induces a down-regulation of hippocampal 5-HT6 receptor expression. In human brain tissue, we found that Alzheimer's disease affects to the 5-HT6 expression and to the signal transduction system. Moreover, psychotic symptoms may be related to a dysregulation of the activation of 5-HT6 receptors by 5-ht. important memory disturban.ces in stress-related psychiatric disorders have been associated to an impairment of the hpa axis reactivity. sb-271046 was able to revert cognitive disturbances associated to a model of maternal separation. Finally, we demonstrate that 5-HT6 receptor modulates hpa function. These results suggest that pharmacological modulation of 5-HT6 receptor could be of interest in the treatment of cognitive dysfunction characterized by a cholinergic hypofunction (Alzheimer's disease) and neuropsychiatric disorders, such as schizophrenia and depression