title: 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.
authors: Departamento De Fisiología, Escuela Nacional De Ciencias Biológicas, Instituto Politécnico Nacional, México, D. F., México; Programa Educativo De La Licenciatura En Terapia Física, Universidad Politécnica De Pachuca, Zempoala, Hidalgo, México.
authors: Blanca Estela
authors: BE
authors: Jaramillo-Loranca
authors: Linda
authors: L
authors: Garcés-Ramírez
authors: Alicia Angélica
authors: AA
authors: Munguía Rosales
authors: Carolina
authors: C
authors: Luna Ramírez
authors: Genaro
authors: G
authors: Vargas Hernández
authors: Oscar
authors: O
authors: Morales-Dionisio
authors: Kateri
authors: K
authors: González-Elizalde
authors: Gonzalo
authors: G
authors: Flores
authors: Sergio
authors: S
authors: Zamudio
authors: Fidel
authors: F
authors: De La Cruz-López
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D005106:Exploratory Behavior / Q000187:drug effects; D006146:Guanidines / Q000627:therapeutic use*; D006624:Hippocampus / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D065808:Prepulse Inhibition / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects; D016622:Silver Staining
chemical_list: D000927:Anticonvulsants; D006146:Guanidines; C050232:1,3-ditolylguanidine
keywords: DTG; Golgi-Cox; neonatal ventral hippocampal lesion; schizophrenia; sigma receptor