Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions...
Recent studies have implicated the endogenous opioid system in the antidepressant actions of ketamine, but the underlying mechanisms remain unclear. We used a combination of pharmacological, behavioral, and molecular approaches in rats to test the contribution of the prefrontal endogenous opioid system to the antidepressant-like effects of a single dose of ketamine. Both the behavioral actions...
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is the prototype for a potential new generation of glutamate-based antidepressants that rapidly relieve symptoms of depression within hours of treatment. Studies in rodents have demonstrated that neuroplasticity in the medial prefrontal cortex (mPFC) is critical for the antidepressant actions of ketamine. However, effector circuits...
A single subanesthetic dose of ketamine exerts rapid antidepressant‐like effects via rapid glutamate efflux, activation of mTORC1 signaling, and enhanced synaptic transmission in the medial prefrontal cortex (mPFC); however, the initial cellular trigger for these synaptic and behavioral actions of ketamine still remains unclear. Here, we used electrophysiology, biochemistry, molecular biology...
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes,...
Ketamine produces rapid and sustained antidepressant actions in depressed patients, but the precise cellular mechanisms underlying these effects have not been identified. Here we determined if modulation of neuronal activity in the infralimbic prefrontal cortex (IL-PFC) underlies the antidepressant and anxiolytic actions of ketamine. We found that neuronal inactivation of the IL-PFC completely...