Antidepressant drugs and psychotherapy combined are more effective in treating mood disorders than either treatment alone, but the neurobiological basis of this interaction is unknown. To investigate how antidepressants influence the response of mood-related systems to behavioral experience, we used a fear-conditioning and extinction paradigm in mice. Combining extinction training with chronic fluoxetine, but neither treatment alone, induced an enduring loss of conditioned fear memory in adult animals. Fluoxetine treatment increased synaptic plasticity, converted the fear memory circuitry to a more immature state, and acted through local brain-derived neurotrophic factor. Fluoxetine-induced plasticity may allow fear erasure by extinction-guided remodeling of the memory circuitry. Thus, the pharmacological effects of antidepressants need to be combined with psychological rehabilitation to reorganize networks rendered more plastic by the drug treatment.
Tuesday, January 03, 2012
Have a scary memory? Erase it with prozac plus psychotherapy.
Numerous clinical studies by now have shown that a combination of antidepressant medication and psychological treatment works better for mood disorders than either therapy on its own. Karpova et al. have now ferreted out the mechanisms that might underlie this fact by investigating the effect of fluoxetine (Prozac) on fear-conditioned memories in mice. Fluoxetine accelerated extinction of fear responses, and together with extinction training disrupted fear renewal and fear reinstatement, but neither treatment by itself produced long term fear extinction. Their results suggest that fluoxetine reactivates plasticity within the amygdala, which, in combination with extinction training, can lead to the erasure of conditioned fear responses. Here is their abstract: