ABSTRACT
It has been suggested that hyperglycemia and insulin resistance triggered by energy-dense diets can account for hippocampal damage and deficits of cognitive behaviour. We wonder if the impairment of learning and memory processes detected in diet-induced obese (DIO) mice is linked to diet composition itself. With this purpose we have evaluated learning performance in mice undergoing a short-term high-fat (HF) treatment, which leads to a pre-obese state characterized by increased adiposity without significant changes of glucose and insulin plasma levels. C57BL/6J mice were fed either a HF (45 kcal% from fat) or control diet (10 kcal% from fat) during 8 weeks. Learning performance was evaluated by using the four-arm baited version of the eight-arm radial maze test (RAM). Mice were trained to learn the RAM protocol and then memory was tested at different time-points. Time spent to consume food placed in baited arms and errors committed to find them were measured in all sessions. DIO mice significantly spent more time in learning the task and made a greater number of errors than controls. Moreover, retention tests revealed that both working and total memory errors were also more numerous in DIO mice. The current results show that short-term DIO impairs spatial learning and suggest that impairment of hippocampal learning elicited by HF diets might be perceptible before metabolic alterations linked to obesity develop.
Subject(s)
Adiposity/physiology , Diet , Dietary Fats , Maze Learning/physiology , Obesity/physiopathology , Spatial Behavior/physiology , Analysis of Variance , Animals , Body Weight/physiology , Eating/physiology , Insulin/blood , Leptin/blood , Male , Mice , Radioimmunoassay , Space Perception/physiologyABSTRACT
Introducción. La administración crónica de fluoxetina en ratas origina un incremento en el número de células nerviosas que expresan el receptor opioide mu en diversas regiones prosencefálicas, siguiendo un patrón muy parecido al desencadenado por la administración de imipramina. Objetivo. Este trabajo pretende describir los efectos de la administración crónica de sertralina sobre el inmunomarcaje de receptores opioides mu en diversas regiones prosencefálicas de la rata y comparar su acción con la ejercida por la fluoxetina. Material y métodos. Se emplearon ratas tratadas por vía intraperitoneal con el fármaco, utilizándose posteriormente un método inmunocitoquímico y un equipo de análisis de imagen para determinar el número de células nerviosas por unidad de superficie que expresaban el receptor opioide mu en las regiones prosencefálicas estudiadas. Resultados. Aunque la administración crónica de sertralina en ratas genera un incremento estadísticamente significativo en el número de células nerviosas que expresan el receptor opioide mu en el caudado putamen, el giro dentado, el septo lateral y las cortezas frontal, parietal y piriforme, existen algunas ligeras diferencias regionales en su acción con respecto a lo descrito anteriormente para el caso de la fluoxetina, tales como un mayor efecto de la sertralina sobre la corteza parietal y el septo y una acción menos intensa sobre la corteza frontal. Conclusión. Las diferencias regionales observadas en la acción de la sertralina (con respecto a fluoxetina) sobre la expresión del receptor opioide mu en el prosencéfalo de la rata podrían relacionarse con una menor incidencia de efectos adversos de tipo psicomotor (AU)
Subject(s)
Rats , Animals , Male , Septum Pellucidum , Receptors, Opioid, mu , Selective Serotonin Reuptake Inhibitors , Rats, Sprague-Dawley , Parietal Lobe , Neurons , Sertraline , Immunohistochemistry , Fluoxetine , Frontal Lobe , TelencephalonABSTRACT
Lithium can potentiate the effects of antidepressant drugs and alters morphine analgesia and phosphoinositide turnover. Analysis of mu-opioid receptor immunostaining after chronic lithium administration in rats revealed an increase in the density of cells expressing mu-opioid receptors in the caudatus-putamen, the dentate gyrus, the lateral septum and the frontal, parietal and piriform cortices. These data suggest that mu-opioid receptor expression in the rat forebrain is altered by in vivo chronic lithium treatment. This could be a compensatory mechanism, induced in part by the effects of lithium on mu-opioid receptor transduction mechanism.
Subject(s)
Brain Chemistry/drug effects , Brain/drug effects , Lithium/pharmacology , Receptors, Opioid, mu/drug effects , Animals , Brain/cytology , Brain/metabolism , Male , Neurons/drug effects , Neurons/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/analysis , Receptors, Opioid, mu/metabolismABSTRACT
INTRODUCTION: Chronic fluoxetine or imipramine administration in rats can generate a similar increase in the number of neural cells immunostained for mu opioid receptors in several prosencephalic regions. OBJECTIVE: The aim of the present work was to describe the effects of chronic sertraline administration on mu opioid receptor immunostaining in several rat brain prosencephalic regions, in order to compare with previously described fluoxetine effects. MATERIALS AND METHODS: Experimental animals were chronically administered with sertraline (i.p.). An immunocytochemical method, with the aid of a computerized image analysis system, was used in order to measure the number of neural cells immunostained for mu opioid receptors in several prosencephalic regions. RESULTS: Although chronic sertraline administration in rats generates a significant increase in the number of neural cells immunostained for mu opioid receptors in the caudatus-putamen, dentate gyrus, lateral septum and the frontal, parietal and piriform cortices, slight regional differences, with respect to fluoxetine action, were found. Thus, a more marked action on parietal cortex and lateral septum, and a lesser action on the frontal cortex, were found. CONCLUSION: Regional differences in sertraline effects, with respect to fluoxetine, could be related to a lesser incidence of psychomotor impairment.
Subject(s)
Brain/drug effects , Fluoxetine/pharmacology , Receptors, Opioid, mu/metabolism , Selective Serotonin Reuptake Inhibitors/pharmacology , Sertraline/pharmacology , Animals , Brain/metabolism , Fluoxetine/administration & dosage , Frontal Lobe/drug effects , Immunohistochemistry , Male , Neurons/drug effects , Parietal Lobe/drug effects , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/drug effects , Septum Pellucidum/drug effects , Selective Serotonin Reuptake Inhibitors/administration & dosage , Sertraline/administration & dosageABSTRACT
Fluoxetine is a selective serotonin reuptake inhibitor. Analysis of mu-opioid receptor immunostaining after chronic fluoxetine administration in rats revealed an increase in the density of cells expressing mu-opioid receptors in the caudatus-putamen, the dentate gyrus, the lateral septum and the frontal, parietal and piriform cortices. These data suggest that mu-opioid receptor expression in the rat forebrain is altered by in vivo chronic fluoxetine treatment.
Subject(s)
Fluoxetine/pharmacology , Prosencephalon/drug effects , Receptors, Opioid, mu/analysis , Selective Serotonin Reuptake Inhibitors/pharmacology , Animals , Immunohistochemistry , Male , Prosencephalon/chemistry , Rats , Rats, Sprague-DawleyABSTRACT
Imipramine hydrochloride (CAS 113-52-0) is a widely used antidepressant and can interact with opioid receptors. However, complete information concerning possible regional alterations in mu-opioid receptor expression in the rat forebrain after chronic treatment with this substance is still lacking. This being the case, analysis of mu-opioid receptor immunostaining in several regions of the rat brain after imipramine administration in vivo was made, and an increase in the density of cells expressing mu-opioid receptors in the caudatus-putamen, the dentate gyrus and the frontal, parietal and piriform cortices after chronic imipramine treatment, with respect to controls, was found. These data suggest that mu-opioid receptor expression in the rat forebrain is altered by in vivo chronic imipramine treatment.