Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy
Neuropsychopharmacology March 5, 2015 Sarah A. Stuart, Paul Butler, Marcus R. Munafò et al. 73 citations
Antidepressant drugs like ketamine and venlafaxine modify emotional biases in rats, but through different brain regions and at different times. In a bowl-digging task, rats learned two equal-value experiences, one under an affective manipulation and one under control conditions; their later choices revealed an affective bias. Ketamine, which acts rapidly, reduced a previously acquired negative bias when given before the preference test, and its effect depended on the medial prefrontal cortex. Venlafaxine, which acts slowly, induced a positive bias when given before learning, and its effect depended on the amygdala. Increasing the number of substrate-reinforcer associations amplified both positive and negative biases. This pattern may explain why venlafaxine has a delayed onset of action while ketamine acts quickly but lacks long-term efficacy.