The authors of this study were keen to note that combined antidepressant and psychotherapy treatments are more effective in treating mood disorders than either treatment alone. To investigate how antidepressants influence such behavioral response to emotional experience, they conducted a fear-conditioning and extinction experiment in mice**.Combining a behavioral method (extinction training) with antidepressant treatment (chronic fluoxetine) induced an enduring loss of conditioned fear memory in adult mice. Neither treatment alone had the desired effect. The authors hypothesized that fluoxetine treatment increased neuronal synaptic plasticity, converting the fear memory circuitry into a more immature state. The combination with psychological rehabilitation may produce the desired remodeling of brain memory circuits. Fluoxetine-induced plasticity may allow fear erasure by extinction-guided remodeling of the memory circuitry. Thus, the pharmacological effects of antidepressants may benefit from combination with psychological rehabilitation to reorganize networks rendered more plastic by the drug treatment. Brain-derived neurotrophic factor (BDNF) may be involved.


Karpova NN et al.: Fear erasure in mice requires synergy between antidepressant drugs and extinction training. Science 334(6063):1731-1734 (December 2011).

[** = A simple example of fear conditioning is when an aversive stimulus such as electric shock is presented in a particular environment, resulting in fearful emotional response whenever the individual is re-exposed to that environment].

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