Ketamine rescues anhedonia by cell-type- and input-specific adaptations in the nucleus accumbens.
Neuron May 7, 2025 Federica Lucantonio, Jacob Roeglin, Shuwen Li et al. 24 citations
Ketamine rapidly and sustainably alleviates anhedonia, a core symptom of depression, by restoring weakened excitatory synapses onto D1-medium spiny neurons in the nucleus accumbens of chronically stressed mice. Artificially strengthening these synapses reproduces ketamine's behavioral benefits, while blocking the synaptic restoration prevents the therapeutic effect. The relevant synaptic inputs originate from the medial prefrontal cortex and ventral hippocampus.