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

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.
AuthorsBlanca Estela Jaramillo-Loranca, Linda Garcés-Ramírez, Alicia Angélica Munguía Rosales, Carolina Luna Ramírez, Genaro Vargas Hernández, Oscar Morales-Dionisio, Kateri González-Elizalde, Gonzalo Flores, Sergio Zamudio, Fidel De La Cruz-López
JournalSynapse (New York, N.Y.) (Synapse) Vol. 69 Issue 4 Pg. 213-25 (Apr 2015) ISSN: 1098-2396 [Electronic] United States
PMID25682743 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2015 Wiley Periodicals, Inc.
Chemical References
  • Anticonvulsants
  • Guanidines
  • 1,3-ditolylguanidine
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Anticonvulsants (therapeutic use)
  • Behavior, Animal (drug effects)
  • Brain Injuries (drug therapy, pathology, physiopathology)
  • Exploratory Behavior (drug effects)
  • Guanidines (therapeutic use)
  • Hippocampus (pathology, ultrastructure)
  • Male
  • Motor Activity (drug effects)
  • Prepulse Inhibition (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Reflex, Startle (drug effects)
  • Silver Staining

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