Effects of co-administration of amitriptyline and fluoxetine on inhibitory avoidance in mice.

We have previously observed that, while the impairing effects of amitriptyline on inhibitory avoidance in mice are consistently observed, those of acute fluoxetine are negligible. Two experiments were designed to investigate whether a regular dose of fluoxetine potentiates the effect of a low dose of amitriptyline that is ineffective when administered alone. Male and female CD1 mice were administered i.p. 30 min before training, as follows. In the first experiment, they were injected with saline, one of three doses of amitriptyline (2.5, 5, 10mg/kg), one dose of fluoxetine (15 mg/kg), or a combination of amitriptyline (2.5mg/kg) and fluoxetine (15 mg/kg). In the second experiment, the mice were injected with saline, amitriptyline (2.5mg/kg), one of three doses of fluoxetine (10, 15, 20mg/kg), or a combination of 2.5mg/kg of amitriptyline and one of the three mentioned doses of fluoxetine. Drug doses were selected based on previous experiments in our laboratory reported in other publications. The behavioural procedure used to test the effects of these treatments was step-through inhibitory avoidance. The joint administration of amitriptyline 2.5mg/kg and fluoxetine 15 mg/kg had a clear impairing effect on inhibitory avoidance as observed in the two experiments. The dose of 2.5mg/kg of amitriptyline, given alone, was ineffective. Doses of 5mg/kg, or higher, of amitriptyline impaired inhibitory avoidance. The only effect detected when fluoxetine was administered separately was in the males of the experiment 1, which exhibited less avoidance than controls. Our preclinical research throws light on the benefits of the combined administration of antidepressants.

The effect of amitriptyline on inhibitory avoidance in mice is dose-dependent.

The purpose of the present work was to study the dose-effect relationship of the antidepressant amitriptyline on inhibitory avoidance in male and female mice. Subjects received physiological saline or 2.5, 5, 10 or 20 mg/kg of amitriptyline hydrochloride 30 min before the training phase, and were subjected to the test phase 24 h later. Results showed a clear impairing effect of amitriptyline on inhibitory avoidance in both male and female mice, and that the effect is dose-dependent.

The effect of amitriptyline on inhibitory avoidance in mice is dose dependent / El efecto de la amitriptilina sobre la evitación inhibitoria en ratones es dependiente de dosis

The purpose of the present work was to study the dose-effect relationship of the antidepressant amitriptyline on inhibitory avoidance in male and female mice. Subjects received physiological saline or 2.5, 5, 10 or 20 mg/kg of amitriptyline hydrochloride 30 min before the training phase, and were subjected to the test phase 24 h later. Results showed a clear impairing effect of amitriptyline on inhibitory avoidance in both male and female mice, and that the effect is dose-dependent (AU)

El propósito del presente trabajo fue estudiar la relación dosis-efecto del antidepresivo amitriptilina sobre la evitación inhibitoria en ratones machos y hembras. Los sujetos recibieron suero salino o 2.5, 5, 10 ó 20 mg/kg de clorhidrato de amitriptilina 30 min antes de la fase de entrenamiento, y fueron sometidos a la fase de test 24 h más tarde. Los resultados mostraron un claro efecto deteriorante de la amitriptilina sobre la evitación inhibitoria tanto en los ratones machos como en las hembras, y que el efecto es dependiente de dosis (AU)

Effects of anisomycin on inhibitory avoidance in male and female CD1 mice.

The antibiotic anisomycin inhibits protein synthesis, which much research has suggested is required for the formation of long-term memory. The present work studied the effects of acute subcutaneous administration of anisomycin on the consolidation of memory in an inhibitory avoidance task in CD1 mice of both sexes. The animals were separated by sex and randomly distributed into three groups: two groups were injected with 150 mg/kg anisomycin, one immediately after the training phase and the other 24 h later, while the control group received saline. The interval between training and test was four days. Anisomycin administrated immediately after training produced statistically significant impairment of memory, which was not observed when the drug was administered 24 h after training. No sex differences were observed in the effects of anisomycin. These results extend to female mice the memory impairing effects of anisomycin previously observed in males and endorse the hypothesis that the establishment of long-term memory depends on protein synthesis shortly after training.

Effects of anisomycin on inhibitory avoidance in male and female CD1 mice / Efectos de la anisomicina sobre la evitación inhibitoria en ratones CD1 machos y hembras

The antibiotic anisomycin inhibits protein synthesis, which much research has suggested is required for the formation of long-term memory. The present work studied the effects of acute subcutaneous administration of anisomycin on the consolidation of memory in an inhibitory avoidance task in CD1 mice of both sexes. The animals were separated by sex and randomly distributed into three groups: two groups were injected with 150 mg/kg anisomycin, one immediately after the training phase and the other 24 h later, while the control group received saline. The interval between training and test was four days. Anisomycin administrated immediately after training produced statistically significant impairment of memory, which was not observed when the drug was administered 24 h after training. No sex differences were observed in the effects of anisomycin. These results extend to female mice the memory impairing effects of anisomycin previously observed in males and endorse the hypothesis that the establishment of long-term memory depends on protein synthesis shortly after training (AU)

El antibiótico anisomicina inhibe la síntesis de proteínas, la cual muchos estudios indican que es necesaria para la formación de la memoria a largo plazo. En el presente trabajo se estudiaron los efectos de la administración aguda subcutánea de anisomicina sobre la consolidación de la memoria en una tarea de evitación inhibitoria en ratones CD1 de ambos sexos. Los animales fueron separados por sexo y distribuidos al azar en tres grupos: dos grupos fueron inyectados con 150 mg/kg de anisomicina, uno inmediatamente después de la fase de entrenamiento y el otro 24 h después, mientras que el grupo control recibió suero salino. El intervalo entre el entrenamiento y el test fue de cuatro días. La anisomicina administrada inmediatamente después del entrenamiento produjo un deterioro de memoria estadísticamente significativo, deterioro que no fue observado cuando el fármaco fue administrado 24 h después del entrenamiento. No se observaron diferencias de sexo en los efectos de la anisomicina. Estos resultados extienden a las hembras los efectos deteriorantes de la anisomicina sobre la memoria previamente observados en machos y respaldan la hipótesis de que el establecimiento de la memoria a largo plazo depende de la síntesis de proteínas poco después del entrenamiento (AU)

Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?

State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 x 2 experimental design. The results do not show SDL in any of the drugs. In the case of amitriptilyline, the data can be attributed to a memorization deficit, while the maprotiline results are interpreted as simultaneously influenced by memorization deficit and performance facilitation due to motor impairment. Fluoxetine treatment did not produce any deteriorating effect on the conditioning. Drugs had some different effects on the performance of males and females, males showing a slightly higher deterioration than females with administration of amitriptyline and maprotiline. This study shows that these antidepressants affect the acquisition/consolidation but not the retrieval process in the inhibitory avoidance learning.

La maprotilina anula las diferencias entre ratones machos y hembras en el laberinto de agua de Morris / Maprotiline removes differences between male and female mice in the Morris water maze

Se estudiaron los efectos de la administración subcrónica de maprotilina (15, 20 y 25 mg/kg) sobre el aprendizaje espacial con el laberinto de agua de Morris, así como sobre la actividad general, en ratones machos y hembras. En la dase de adquisición, la administración de maprotilina (15 y 25 mg/kg) deterioró el aprendizaje en los machos pero no en las hembras, y no se observaron diferencias de sexo en el grupo control. En la fase de retención, la maprotilina, en las tres dosis, anuló las diferencias de sexo. Sobre la actividad general, la maprotilina, en las tres dosis, tuvo un efecto supresor de la misma y anuló las diferencias de sexo. El efecto sexodimórfico del fármaco en la fase de adquisición están en la línea del encontrado en otros experimentos, en los que se han usado otros fármacos, tanto antidepresivos como antipsicóticos, y otras tareas de aprendizaje en ratones. Este sexodimorfismo consiste en que el efecto del fármaco se observa sólo en los machos o, si se observa en los dos sexos, es mayor en los machos que en las hembras. La anulación de las diferencias de sexo en la fase de retención puede ser debida a la acción anticoligérnica de la maprotilina (AU)

The effects of subchronic administration of maprotiline (15, 20 and 25 mg/kg) on spatial learning, utilising the Morris water maze, and on general activity were assessed in male and female mice. In the acquisition phase, maprotiline (15 and 25 mg/kg) impaired learning in males but not in females. Also in this phase, sex differences were not found in the control group. In the retention phase, all three levels of maprotiline removed the sex differences found in the control group. In the general activity test, all three doses of maprotiline decreased activity and removed the sex differences found in the control group. Sexual dimorphism in the effects of maprotiline on spatial learning agrees with findings in studies of the effects of antidepressants and antipsychotics on different learning tasks in mice. When this dimorphism is present, the drug effect is observed only in males or, if present in males and females, it is stronger in the former. The absence of sex differences in the maprotiline treated groups in the retention phase could be due to the anticholinergic properties of the drug (AU)