Correo Electrónico
DNINFOA - SIA
Bibliotecas
Convocatorias
Identidad U.N.
Publicado
Efecto de la alopregnanolona sobre la ansiedad en ratas con separación materna durante la lactancia
The effect of allopregnanolone on anxiety induced in rats separated from their young during breastfeeding
Palabras clave:
Separación materna, Alopregnanolona, Laberinto en Cruz Elevado, Estrés Fisiológico, Ansiedad, Receptores de GABA A, Acido gamma-aminobutírico, Conducta (es)Maternal Separation, GABA A receptor, allopregnanolone, elevated plus maze, stress, Anxiety, Receptors, GABA, gamma-Aminobutyric acid, Behavior (en)
Antecedentes. La relación madre-hijo y el cuidado parental al recién nacido son fundamentales en el desarrollo fisiológico y emocional de los individuos. Evidencias asocian el estrés temprano con el desarrollo de enfermedades mentales. El modelo de separación materna durante la lactancia (SMDL) se ha utilizado para inducir estrés temprano en ratas y estudiar efectos a largo plazo. Diversos estudios han encontrado que, en ratas separadas de sus madres, disminuyen los niveles del receptor GABA-A y esos bajos niveles están asociados a comportamientos ansiosos.
Objetivo. Evaluar el efecto de la alopregnanolona, un neuroesteroide agonista del receptor GABA-A, sobre la ansiedad inducida por SMDL.
Materiales y métodos. Se utilizaron 30 ratas Wistar dividas en dos grupos, uno control y uno experimental (SMDL). La SMDL se realizó desde el día postnatal 1 hasta el día postnatal 21, durante 180 minutos en la mañana y 180 minutos en la tarde. Desde el día 22 los sujetos se alojaron en cajas por sexo y tratamiento y continuaron su desarrollo normal hasta el día 60, en el que se hizo la inyección con alopregnanolona y la prueba comportamental en el laberinto en cruz elevado.
Resultados. El estrés crónico causado por la SMDL afecta el comportamiento de los individuos, perfil comportamental que varía dependiendo del sexo. Se encontró que los machos presentan comportamientos más ansiosos que las hembras, las cuales a su vez muestran más actividad locomotora y exploración
Conclusiones. Al aplicar alopregnanolona el repertorio comportamental varía en los animales con SMDL; estos resultados sugieren que la alopregnanolona, a través de su unión al receptor GABA-A, puede llegar a revertir los efectos de la separación materna, sobre los comportamientos relacionados con ansiedad.
Background. The mother-child relationship and parental care for the newborn are fundamental in individuals' physiological and emotional development. Evidence-based research associates early stress with the development of mental illnesses. Maternal separation during lactation (MSDL) models have been used to induce early stress in rats and for studying the long-term effects of such intervention. Several studies have found decreased GABA-A receptor levels in separated rats from their mothers and such low levels have been associated with anxious behaviour.
Objective. Assessing the effect of allopregnanolone (a GABA-A receptor neurosteroid agonist) on MSDL-induced anxiety.
Materials and methods. Thirty Wistar rats were divided into two groups: control and experimental (MSDL). SMDL occurred for 180 minutes in the morning and 180 minutes in the afternoon. Subjects were housed in boxes by gender and treatment following day 22 and their normal development was allowed to continue until day 60 when they were injected with allopregnanolone and underwent a behavioural test in an elevated plus maze (EPM).
Results. Chronic stress induced by MSDL affected individuals' behaviour, their behavioural profile varying according to their gender. Males exhibited more anxious behaviour than females who engaged in more locomotive and exploratory activity.
Conclusions. MSDL animals' behavioural repertoire varied due to the allopregnanolone injection, suggesting that the effect of allopregnanolone due to GABA-A receptor interaction could reverse the effects of maternal separation on anxiety-related behaviour.
Descargas
Citas
Law AJ, Pei Q, Feldon J, Pryce CR, Harrison PJ. Gene expression in the anterior cingulate cortex and amygdala of adolescent marmoset monkeys following parental separations in infancy. Int J Neuropsychopharmacol. 2009;6:761-72.
Helmeke C, Poeggel G, Braun K. Differential emotional experience induces elevated synaptic densities on basal dendrites of piramidal neurons in the anterior cingulate cortex of Octo-dondegus. Neuroscience. 2001;104:927-31.
Gilmer W & McKinney W. Early Experience and depressive disorders: Human and non-human primate studies. J Affect Disord. 2003;75:97-113.
Levine S. The effects of differential infantile stimulation on emotionality at weaning. Can J Psychol. 1959;13:243-7.
Camargo-Ramos CM, Pinzón-Villate GY. La Promoción de la Salud en la Primera Infancia: Evolución del concepto y su aplicación en el contexto internacional y nacional. rev.fac.med. 2012;60:62-74.
Heim C, Newport DJ, Miller AH, Nemeroff CB. Long-term neuroendocrine effects of childhood maltreatment. JAMA. 2000;284:2321.
Moreno-Hernández L, Lamprea M, Dueñas, Z. Early Maternal separation (EMS) affects differentially anxiolytic behavior on male and female rats. Annual Meeting. Neurosciences. 2007;P-841.5.
Kolb B, Ian Q. Neuropsicología Humana. Ed. Médica Panamericana; 2006.
Moreno-Hernández L, Lamprea M, Dueñas Z. Diferencias en los comportamientos asociados con la ansiedad de ratas macho y hembra expuestas a un protocolo de estrés crónico por separación maternal temprana. Suma Psicológica. 2009;16:31-43.
León DA. Aproximación preliminar al estudio de los mecanismos que inducen ansiedad en ratas que han sufrido estrés postnatal. Tesis de Maestría en Neurociencias. Universidad Nacional; 2010.
Slotten HA, Kalinichev M, Hagan JJ, Marsden CA, Fone KC. Long-lasting changes in behavioural and neuroendocrine indices in the rat following neonatal maternal separation: gender-dependent effects. Brain Res. 2006;1097:123-32.
Rodríguez-Landa JF, Contreras CM. Algunos datos recientes sobre la isiopatología de los trastornos por ansiedad. Annu Rev Biomed. 1998;9:181-91.
Carobreza AP, Bertogliob LJ. Ethological and temporal analyses of anxiety-like behavior: The elevated plus-maze model 20 years on. Neurosci Biobehav Rev. 2005;29:1193-205.
Bowen CA, Gatto GJ, Grant KA Assessment of the multiple discriminative stimulus effects of ethanol using an ethanol-pentobarbital-water discrimination in rats. Behav Pharmacol. 1997;8:339-52.
Torres SJ, Nowson CA. Relationship between stress, eating behavior, and obesity. Nutrition. 2007;23:887-94.
Jiménez-Vasquez PA, Mathe AA, Thomas JD, Riley EP, Ehlers CL. Early maternal separation alters neuropeptide Y concentrations in selected brain regions in adult rats. Brain Res Dev Brain Res. 2001;131:149-52.
Rhees RW, Lephart ED & Eliason D. Effects of maternal separation during early postnatal development on male sexual behavior and female reproductive function. Behav Brain Res. 2001;123:1-10.
Cirulli F, Micera A, Alleva E, Aloe L. Early maternal separation increases NGF expression in the developing rat hippocampus. Pharmacology Biochemistry and Behavior. 1998;59:853-8.
Lehmann J, Pryce CR, Bettschen D,Feldon J. The maternal separation paradigm and adult emotionality and cognition in male and female Wistar rats. Pharmacology Biochem Behav. 1999;64(4):705-15.
León DA, Dueñas Z. Effects of early maternal separation on the performance in the elevated plus maze in adult rats. Actabiológi-cacolombiana. 2012;17:129-42.
Beleboni RO, Carolino RO, Pizzo AB, Castellan-Baldan L, Coutinho-Netto J, dos Santos WF, Coimbra NC. Pharmacological and biochemical aspects of GABAergic neurotransmission: pathological and neuropsychobiological relationships. Cell Mol-Neurobiol. 2004;24:707-28.
Macdonald RL, Gallagher MJ, Feng HJ, Kang J. GABA(A) receptor epilepsy mutations. Biochem Pharmacol. 2004;68:1497-506.
Chica HL. Relación entre los Trastornos por Ansiedad y Alteraciones del Oído Interno. rev.fac.med. 2010;58:60-70.
Jonas JM, Cohon MS. A comparison of the safety and efficacy of alprazolam versus other agents in the treatment of anxiety, panic and depression: a review of the literature. J Clin Psychiatry. 1993;54:25-48.
Díaz R. The Neurosteroid 3a-Hydroxy-5a-Pregnan-20-One Induces Cytoarchitectural Regression in Cultured Fetal Hippocampal Neurons. J Neurosci. 1994;14:2763-74.
Pellow S, Chopin P, File Se, Briley M. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985;14:149-67.
Roman E, Gustafsson L, Berg M, Nylander I Behavioral profiles and stress-induced corticosteroid secretion in male Wistar rats subjected to short and prolonged periods of maternal separation. Horm Behav. 2006;50:736-47.
Blanchard DC, Griebel G, Blanchard RJ. Gender bias in the preclinical psychopharmacology of anxiety: Male models for (predominantly) female disorders. J Psychopharmacol. 1995; 9:79-82.
Marín MT, Planeta CS. Maternal separation affects cocaine-induced locomotion and response to novelty in adolescent, but not in adult rats. Bain Res.2004;1013:83-90.
Licencia
Derechos de autor 2014 Revista de la Facultad de Medicina
Esta obra está bajo una licencia Creative Commons Reconocimiento 3.0 Unported.
-
