Ketamine selectively enhances AMPA neurotransmission onto a subgroup of identified serotoninergic neurons of the rat dorsal raphe

It has been shown repeatedly that the old drug ketamine is able to induce a rapid (within
hours to days) antidepressant effect in otherwise treatment-resistant depressive patients.
Despite many preclinical studies, the exact mechanism and precise site of action of
ketamine is a matter of debate. Because an hypoactivity of brain dorsal raphe nucleus
(DRN) serotonergic neurons has been strongly associated with the pathophysiology of
depressive disorders, we tested the hypothesis that ketamine may rapidly enhance the
activity of these neurons in a brain slice model. In a first step, we examined whether the
drug and one of its possibly important metabolites, hydroxynorketamine (HNK) may alter
the excitatory synaptic drive onto these neurons.