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Abstract Introduction In rats, long-term ovariectomy results in low concentrations of steroid hormones and reproduces anxiety- and depression-like behavior after surgical menopause in women. Progesterone produces antidepressant-like effects two weeks post-ovariectomy (i.e., early post-ovariectomy) through actions on γ-aminobutyric acid-A (GABAA) receptors, but its antidepressant-like effects and mechanism of action in rats eight weeks post-ovariectomy (i.e., late post-ovariectomy, considered a model of surgical menopause) remain unknown. Objective To explore the antidepressant-like effects of progesterone and the participation of GABAA receptors in rats eight weeks post-ovariectomy. Method Long-term ovariectomized female Wistar rats were treated sub-acutely with vehicle or progesterone (.5, 1, and 2 mg/kg) and subjected to the open field and forced swim tests, and behavior was compared with cycling or fluoxetine-treated rats. The rats were then pretreated with picrotoxin (1 mg/kg) followed by progesterone (1 mg/kg) to explore the role of GABAA receptors in long-term-induced depression-like behavior. Results Long-term ovariectomized rats exhibited depression-like behavior in the forced swim test compared with intact rats, an effect that was not observed in progesterone- and fluoxetine-treated long-term ovariectomized rats. These effects were not attributable to psychomotor alterations. In the open field test, the time spent rearing and grooming was lower in ovariectomized rats compared with intact rats, which was not observed in progesterone- and fluoxetine-treated rats. Picrotoxin blocked the effects of progesterone in both behavioral tests. Discussion and conclusion These results indicated that sub-acute progesterone treatment reduced depression-like behavior through actions on GABAA receptors in a rat model of surgical menopause.
Resumen Introducción En la rata, la ovariectomía a largo plazo reproduce algunos síntomas de la menopausia quirúrgica, incluyendo la conducta de tipo depresiva. La progesterona produce efectos tipo antidepresivo en ratas con dos semanas de post-ovariectomía (post-ovariectomía temprana) con participación del receptor GABAA, pero se desconoce si este efecto y mecanismo de acción se mantiene en ratas con ocho semanas de post-ovariectomía (post-ovariectomía tardía considerada como un modelo de menopausia quirúrgica). Objetivo Evaluar el efecto tipo antidepresivo de la progesterona y la participación del receptor GABAA en ratas con ocho semanas de post-ovariectomía. Método Ratas con ocho semanas de post-ovariectomía fueron tratadas sub-agudamente con vehículo o progesterona (.5, 1, y 2 mg/kg) y comparadas con ratas intactas u ovariectomizadas tratadas con fluoxetina, evaluadas en campo abierto y nado forzado. Posteriormente, se identificó la participación del receptor GABAA en los efectos de progesterona (1 mg/kg) mediante el pretratamiento con picrotoxina (1 mg/kg). Resultados En nado forzado, la ovariectomía produjo conductas tipo depresión en comparación con las ratas intactas de la gónada, un efecto prevenido por la administración de progesterona y fluoxetina. En campo abierto, no hubo cambios significativos en la locomoción, pero la conducta vertical y el acicalamiento fueron bajos en las ratas ovariectomizadas respecto a las ratas intactas; lo cual fue prevenido por progesterona y fluoxetina. La picrotoxina bloqueó los efectos de la progesterona en ambas pruebas conductuales. Discusión y conclusión El tratamiento subagudo con progesterona reduce la conducta tipo depresión inducida en un modelo de menopausia quirúrgica con participación del receptor GABAA.
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Introducción. El vínculo materno es fundamental para el establecimiento y mantenimiento de las redes sinápticas, y el desarrollo morfofisiológico y emocional de los individuos. Los niños maltratados o rechazados son más propensos a desarrollar psicopatologías. Los modelos animales permiten una aproximación experimental a mecanismos involucrados en alteraciones ocasionadas por estrés temprano. Objetivo. Determinar si la separación materna durante la lactancia, afecta en el adulto el tamaño del cerebro y el número de células inmunorreactivas a la subunidad alfa 1 del recep-tor ácido gamma-aminobutírico: GABA-A. Métodos. Se mantuvieron ratas Wistar con ciclo invertido luz-oscuridad, sin restricciones de agua o comida. Durante la lactancia, a unas mamás les fueron separadas las crías dos veces al día y otras se mantuvieron como grupo control. El día 22 los sujetos se separaron por sexo y tratamiento. El día 60 se perfundieron con paraformaldehído, previa anestesia, y los cere-bros fueron extraídos y pesados. Para identificar el tamaño cerebral, se hicieron cinco cortes seriados de 20 µm cada 100 µm. Se tomaron fotografías y se utilizó una escala micrométrica. La inmunorreacción al receptor GABA-A se analizó en cortes de 20 µm mediante tinción por inmunohistoquímica. Resultados. En las ratas adultas, el peso cerebral total de las ratas separadas fue menor. En las hembras separadas se observó reducción estadísticamente significativa en el tamaño del hipocampo. En los machos separados se observó disminución de la marcación para la subunidad alfa1 del receptor GABA-A, en la corteza prefrontal, la amígdala y el hipocampo. Conclusiones. Estos resultados muestran que la separación materna durante la lactancia altera, en ciertas áreas cerebrales del adulto, el tamaño y la inmunorreacción al receptor GABA-A, y que estos cambios son diferentes en hembras y machos
Introduction: The maternal bond is crucial to establish and maintain synaptic networks and for morphophysiological and emotional development of individuals. Neglected or abused kids are more susceptible to develop psychopathologies. Animal models allow an experimen-tal approach to mechanisms involved in alterations due early stress. Objective:To determine if maternal separation during nursing alters brain size in adults and the amount of immunoreactive cells to alpha subunit of GABA-A receptor. Methods: Wistar rats were kept under reverse light-dark cycle with food and water ad libitum. During nursing, pups were separated from their mothers twice a day and other group was used as control. At day 22nd, subjects were separated by gender and treatment. In day 60, subjects were anesthetized and perfused with paraformaldehyde and brains were extracted and weighted. In order to identify brain size, 5 serial slides of 20 µm were made every 100 µm. Pictures were taken and micrometric scale was used. Immunoreactivity to alpha subunit of GABA-A receptor was analyzed in 20 µm slides through immunohistochemistry. Results: In adults, total brain weight of separated rats was inferior thanin the control group. Separated females showed a significant reduction of hippocampus size. In separated males a decrease of immunoreactivity to GABA-A receptor in prefrontal cortex, amygdala and hip-pocampuswas evidenced. Conclusions: These results show that maternal separation during nursing alterssize in some brain areas of adult rats, the immunoreactivity to alpha subunit of GABA-A receptor, and these changes are different between separated females and males.
Sujets)
Animaux , Anxiété , Acide gamma-amino-butyrique , Relations mère-enfant , RatsRésumé
Objective To observe the expression of gamma-amino butyric acid A receptor(GABAA receptor)?3、?1、? subunits in rat flocculus following unilateral labyrinthectomy(UL).Methods 24 wistar rats were randomly divided into two groups.18 animals received unilateral labyrinthectomy while the others maintained labyrinthine well.After removing left labyrinthine,the change of GABAA receptor ?3、?1、? subunits was detected by immunohistochemistry.Results GABAA receptor ?1、? subunits in flocculus was induced on the operated side after unilateral labyrinthectomy.The most expression was on the 1st day flocculus of following UL.The expression is descending from the 3rd day to 7th day flocculus of following UL.The GABAA receptor ?3 subunit immunostaining in flocculus was weak and did not change in the process of vestibular compensation.Conclusion GABAA receptor ?1、? subunits were induced increase in the flocculus after unilateral labyrinthectomy.The alteration in the resting discharge of the central vestibular neurons may be caused by the increase of GABAA receptor ?1、? subunits in the flocculus.But the significance of the change of GABAA receptor ?1、? subunits in the vestibular compensation is still unknown.Our study suggests that GABAA receptor ?3 subunits may not participate in constructing GABAA receptor in the flocculus.