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An analysis of the involvement of monoaminergic mechanisms in the neuropsychotropic effects of neuroglutam

Content Provider	Springer Nature Link
Author	Tyurenkov, I. N. Bagmetova, V. V. Merkushenkova, O. V. Markina, Yu. V. Klodt, P. M. Narkevich, V. B. Kudrin, V. S. Kondrakhin, E. A. Vasil’eva, E. V. Kovalev, G. I.
Copyright Year	2015
Abstract	It is known that neuroglutam (at 26 mg/kg) potentiates stereotypy that is induced by the agonist of postsynaptic dopamine receptors apomorphine (1 mg/kg), and suppresses catalepsy that is induced by the blocker of postsynaptic dopamine receptors haloperidol (1 mg/kg), which points to its stimulatory influence on dopaminergic neurotransmission. Neuroglutam (26 mg/kg) does not affect the contents of noradrenaline and dopamine (DA) in homogenates of rat brain structures; however, it increases the concentration of the metabolites of dopamine 3,4-dioxyphenylacetic acid (DOPAC) in the frontal cortex and homovanillic acid (HVA) in the hippocampus, which points to its positive influence on the rate of DA utilization, and, in addition, an increase in indices that characterize the rate of DA turnover, viz., DOPAC/DA and HVA/DA in the striatum. We used the method of radioligand binding in vitro with [G-$^{3}$H]-sulpiride to show that neuroglutam (10$^{−10}$–10$^{−4}$ M) does not directly interact with dopamine D$_{2}$ receptors; however, during subchronic administration (5 days; a single daily dose of 26 mg/kg) neuroglutam promotes an increase in the density of D2 receptors in the prefrontal cortex, which points to its ability to modulate the expression of these receptors. The data from neurochemical and radioligand analysis suggest that both presynaptic (intensification of metabolic DA turnover) and postsynaptic (DA receptors) mechanisms of dopaminergic neurotransmission are involved in the neuropsychotropic action of neuroglutam. Neuroglutam did not influence the strength of hyperkinesia that was induced by the metabolic precursor of serotonin 5-hydroxytryptophan on the content of serotonin and its metabolites in rat-brain structures and did not alter the receptor binding of [G-$^{3}$H]-ketanserin (an antagonist of 5-HT$_{2A}$ receptors) in the prefrontal cortex both under in vitro conditions and during subchronic administration ex vivo, which points to the absence of direct participation of the serotonergic system in the pharmacological action of the studied drug.
Starting Page	20
Ending Page	28
Page Count	9
File Format	PDF
ISSN	18197124
Journal	Neurochemical Journal
Volume Number	9
Issue Number	1
e-ISSN	18197132
Language	English
Publisher	Pleiades Publishing
Publisher Date	2015-03-06
Publisher Place	Moscow
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	neuroglutam derivatives of glutamic acid dopamine dopaminergic neurotransmission dopamine receptors radioligand binding in vitro and ex vivo Neurosciences
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biochemistry Cellular and Molecular Neuroscience

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