Stress- and antidepressant treatment-induced modifications of 5-HT7 receptor functions in the rat brain

Abstract

Abstract:This paper summarizes a series of electrophysiological studies aimed at finding the effects of the activation of 5-HT 7 receptors on neuronal excitability as well as on excitatory and inhibitory synaptic transmission in the hippocampus and in the frontal cortex of the rat. These studies demonstrated that 5-HT 7 receptors play an important role in the modulation of the activity of the hippocampal network by regulating the excitability of pyramidal cells of the CA1 area, as well as via their effect on GABA and glutamatergic transmission. The reactivity of 5-HT 7 receptors in the hippocampus is decreased by repeated administration of antidepressant drugs and increased by a prolonged high level of corticosterone. More importantly, administration of antidepressant drug, imipramine, prevents the occurrence of corticosterone-induced changes in the function of hippocampal 5-HT 7 receptors. It has also been found that the blockade of 5-HT 7 receptors by the selective antagonist SB 269970, lasting for a few days, causes similar changes to those observed after long-term administration of antidepressants. Thus, it seems that the pharmacological blockade of 5-HT 7 receptors produces faster effects compared to classic antidepressant drugs. A similarity between the changes in the glutamatergic transmission induced by the blockade of 5 HT 7 receptors and those caused by repeated administration of the antidepressant drug, imipramine, has also been found in the frontal cortex. It has also been shown that the changes in glutamatergic transmission and the impairment of long-term synaptic plasticity in the frontal cortex of animals subjected to repeated restraint stress are reversed by the blockade of 5-HT 7 receptors. Overall, these studies, together with the data provided by other investigators, support the hypothesis that 5-HT 7 receptor antagonists may become a prototype of a new class of antidepressant drugs. Such compounds will not function by blocking 5-HT reuptake, as many of the currently used drugs, but through a direct interaction with the 5-HT 7 receptor. This type of action is highly selective and usually does not require the occurrence of adaptive changes in neuronal functions, thus allowing for a much quicker therapeutic effect.

The 5-HT7 receptor antagonist SB 269970 ameliorates corticosterone-induced alterations in 5-HT7 receptor-mediated modulation of GABAergic transmission in the rat dorsal raphe nucleus

“…5-HT 7 receptor blockade has been shown to induce antidepressant-like effects in animal models (reviewed in: Ciranna and Catania 2014 ; Nikiforuk 2015 ). These effects occur faster than those induced by conventional antidepressant drugs (Mnie-Filali et al 2011 ; reviewed in: Tokarski et al 2012a ). We have previously demonstrated that treatment with the selective 5-HT 7 receptor antagonist SB 269970 counteracted repeated restraint stress-induced modifications of glutamatergic transmission and synaptic plasticity in the rat frontal cortex (Tokarski et al 2011 ).…”

5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin

“…A considerable body of experimental evidence indicates that the 5-HT 7 receptor may be involved in the etiology of mental illnesses (reviewed in Hedlund, 2009 ; Ciranna and Catania, 2014 ). Also, recent research has suggested that the antagonists of this receptor may constitute a new class of antidepressant drugs with a faster therapeutic action than that of the currently used drugs (Mnie-Filali et al, 2011 ; reviewed in Tokarski et al, 2012 ).…”

The 5-HT7 receptor as a potential target for treating drug and alcohol abuse

“…Antagonism of 5-HT7Rs can also reverse 5-HT agonist-induced suppression of glutamate release in the DRN and median raphe nucleus (MRN) (Harsing, 2006 ; Pehrson and Sanchez, 2014 ). It has been suggested that there may be 5-HT7 heteroreceptors involved in the inhibition of glutamate release in glutamatergic cortico-raphe projections (Harsing, 2006 ; Duncan and Congleton, 2010 ), whereas 5-HT7R enhancement of 5-HT release may be due to GABA-glutamatergic-serotonergic interactions in the DRN (Harsing et al, 2004 ; Roberts et al, 2004 ; Tokarski et al, 2012 ). More recently, Tokarski et al ( 2011 ) have suggested that 5-HT7R activation may enhance GABAergic transmission in the hippocampus via presynaptic 5-HT7Rs on excitatory glutamatergic input to GABAergic interneurons or activation of post-synaptic 5-HT7Rs on the GABAergic interneurons themselves.…”