Ketamine rapidly reverses stress-induced impairments in GABAergic transmission in the prefrontal cortex in male rodents
| Autor: | Brendan D. Hare, Min Wu, Matthew J. Girgenti, Rosemarie Terwilliger, Emily M. Teichman, Catharine H. Duman, Sriparna Ghosal, Eric S. Wohleb, Rong-Jian Liu, Ronald S. Duman, Manoela V. Fogaça |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Prefrontal Cortex Biology Neurotransmission Inhibitory postsynaptic potential Synaptic Transmission lcsh:RC321-571 03 medical and health sciences 0302 clinical medicine medicine Animals Ketamine Chronic stress Prefrontal cortex lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry gamma-Aminobutyric Acid Neurons Depression Glutamate receptor Antidepressive Agents Mice Inbred C57BL Disease Models Animal 030104 developmental biology nervous system Neurology Inhibitory Postsynaptic Potentials Excitatory postsynaptic potential GABAergic Somatostatin Neuroscience 030217 neurology & neurosurgery Stress Psychological medicine.drug |
| Zdroj: | Neurobiology of Disease, Vol 134, Iss, Pp-(2020) |
| ISSN: | 1095-953X |
| Popis: | Dysfunction of medial prefrontal cortex (mPFC) in association with imbalance of inhibitory and excitatory neurotransmission has been implicated in depression. However, the precise cellular mechanisms underlying this imbalance, particularly for GABAergic transmission in the mPFC, and the link with the rapid acting antidepressant ketamine remains poorly understood. Here we determined the influence of chronic unpredictable stress (CUS), an ethologically validated model of depression, on synaptic markers of GABA neurotransmission, and the influence of a single dose of ketamine on CUS-induced synaptic deficits in mPFC of male rodents. The results demonstrate that CUS decreases GABAergic proteins and the frequency of inhibitory post synaptic currents (IPSCs) of layer V mPFC pyramidal neurons, concomitant with depression-like behaviors. In contrast, a single dose of ketamine can reverse CUS-induced deficits of GABA markers, in conjunction with reversal of CUS-induced depressive-like behaviors. These findings provide further evidence of impairments of GABAergic synapses as key determinants of depressive behavior and highlight ketamine-induced synaptic responses that restore GABA inhibitory, as well as glutamate neurotransmission. |
| Databáze: | OpenAIRE |
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