The sigma agonist 1,3-Di-o-tolyl-guanidine reduces the morphological and behavioral changes induced by neonatal ventral hippocampus lesion in rats

Abstract

Sigma (σ) receptors have generated a great deal of interest due to their possible role in psychosis, neuroprotection, and various other behaviors including addictive processes. Sigma receptors have been located in brain areas involved in motor functions, including the dopaminergic projections from the substantia nigra to the striatum. Evidence suggests that one of their major roles might be to regulate the activity of the glutamatergic system via the N-methyl-D-aspartate receptor. The sigma receptor agonist 1,3-di-o-tolyl-guanidine (DTG) was found to increase dopamine release in the striatum, nucleus accumbens, and prefrontal cortex, in a dose-dependent manner, after central as well as peripheral administration, suggesting a modulatory role of these receptors on the dopaminergic system. The present study examines whether chronic administration of the DTG sigma agonist induces neuromorphological and behavioral changes in neonatal ventral hippocampal lesioned (nVHL) rats as a neurodevelopmental model of schizophrenia. The results show that the DTG administration reduces the hyperlocomotor activity in nVHL rats and reverses the neuronal hypotrophy generated in nVHL rats in the prefrontal cortex, amygdala, and nucleus accumbens. Our results demonstrate that DTG, a sigma-1 receptor agonist, reverses some of the behavioral and neuromorphological effects of nVHL on the rat and supports the possibility that DTG may have beneficial effects in the management of symptoms of schizophrenia.

Screening for Polar Chemicals in Water by Trifunctional Mixed-Mode Liquid Chromatography–High Resolution Mass Spectrometry

“…This chemical is a substance commonly used in polymerization and vulcanization processes in industry, thus likely to occur in water. Since, this compound has also been characterized as having antidepressant properties, 44 it may well have some ecotoxicological relevance and deserves future studies. Some of the remaining chemicals detected are sulfonates.…”

Quantitation of guanidine derivatives as representative persistent and mobile organic compounds in water: method development

“…In view of its acute toxicity to aquatic organisms [13], DPG is classified as a PMT substance and has received considerable attention as an emerging PMOC, as exemplified by its detection in surface water [11,[14][15][16][17][18][19][20][21][22][23]. Similar to DPG, 1,3-di-o-tolylguanidine (DTG) is a guanidine derivative that has been detected in water [2,24,25] and examined in terms of its toxicity [26,27].…”

Role and Therapeutic Potential of Non-coding RNAs in Astrocytes during Neonatal Brain Injury

“…Sigma receptors (σR) are unique drug-binding proteins found in the central nervous system [118], which are located in brain regions involved in motor function, including dopaminergic projections from the substantia nigra to the striatum [119]. The σR 1 agonist DTG reverses behavioral and neuromorphological changes induced by ventral hippocampal lesions in neonatal rats [120]. It was found that circRNA HIPK2 (circ HIPK2) acts as a sponge of miR124-2HG targeting to regulate σR 1 expression and astrocyte activation, which has been shown to attenuate neuroinflammation through the cooperation of cellular autophagy and ER stress [121].…”