Medial orbitofrontal cortex lesion prevents facilitatory effects of d-cycloserine during fear extinction.

Animal models of fear extinction have an important clinical relevance to pharmacological and exposure-based therapies for anxiety disorders. Lesions of prefrontal structures impair fear extinction. On the other hand, d-cycloserine is able to enhance this process. We hypothesize that the integrity of cortical structures involved in inhibitory control of emotional responses is crucial for the facilitatory effects of d-cycloserine. Here, we showed that medial orbitofrontal cortex lesion prevents d-cycloserine enhancement of fear extinction. These preliminary results suggest that effects of pharmacological treatments could be dependent on cortical activity state to promote fear memory reduction.

Efecto de la aplicación aguda de fluoxetina sobre una tarea de miedo condicionado al contexto en ratas sometidas a restricción comportamental / Effect of acute Fluoxetine application on a context fear conditioned task in behaviorally restrained rats Laura A

Para estudiar el efecto del aumento comportamental o farmacológico de la ansiedad sobre la adquisición del miedo condicionado al contexto, 32 ratas Wistar (275±25 gm) divididas en dos grupos (restricción comportamental y control) recibieron fluoxetina (ig, 4 mg/kg; 1ml) o solución salina (ig, 0.9%). Luego fueron entrenadas en una tarea de miedo condicionado al contexto. El ANOVA de dos vías mostró diferencias significativas para el factor tratamiento (F[1,28] = 25.261; P < 0.001). Los sujetos tratados con fluoxetina presentaron menor tiempo de congelamiento (Student Newman-Keuls; P < 0.05). No hubo diferencias significativas para la restricción, ni para la interacción entre factores (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899). Así, la restricción no alteró la adquisición del miedo condicionado indicando que el aumento de liberación de 5-HT así inducido, no es comparable al inducido por fluoxetina. La fluoxetina deterioró la adquisición de la respuesta de miedo, indicando que el mecanismo por el cual la ansiedad interrumpe el aprendizaje puede ser serotoninérgico...

In order to study the effect of behavioral or pharmacologically enhanced anxiety on the acquisition of contextual fear conditioning, thirty two Wistar rats (275±25 gm) were divided in two groups (behavioral restriction and control). Half of each group received saline solution (ig.; 0.9%) or fluoxetine (ig.; 4mg/Kg) before the fear conditioning procedure. The two way ANOVA showed significant differences for treatment (F[1,28] = 25.261; P < 0.001). Student Newman-Keuls showed that subjects treated with fluoxetine had lower freezing times. There were no significant differences nor for restriction neither for the interaction between the factors (F[1,28] = 0.115; P = 0.737 y F[1,28] = 0.016; P = 0.899). Thus, the restriction procedure used did not modify the acquisition of the conditioned fear response suggesting that the putative 5-HT enhancement induced is not comparable to that induced by fluoxetine. Acute fluoxetine disrupted the acquisition of the conditioned fear response, suggesting that the mechanism by means of which anxiety disrupts learning could be serotonergic in nature...