Dopamine-Dependent Ketamine Modulation of Glutamatergic Synaptic Plasticity in the Prelimbic Cortex of Adult Rats Exposed to Acute Stress

多巴胺依赖性氯胺酮对急性应激成年大鼠前额皮质谷氨酸突触可塑性的调节

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作者:Lia Forti, Elona Ndoj, Jessica Mingardi, Emanuele Secchi, Tiziana Bonifacino, Emanuele Schiavon, Giulia Carini, Luca La Via, Isabella Russo, Marco Milanese, Massimo Gennarelli, Giambattista Bonanno, Maurizio Popoli, Alessandro Barbon, Laura Musazzi

Abstract

Traumatic stress is the main environmental risk factor for the development of psychiatric disorders. We have previously shown that acute footshock (FS) stress in male rats induces rapid and long-lasting functional and structural changes in the prefrontal cortex (PFC), which are partly reversed by acute subanesthetic ketamine. Here, we asked if acute FS may also induce any changes in glutamatergic synaptic plasticity in the PFC 24 h after stress exposure and whether ketamine administration 6 h after stress may have any effect. We found that the induction of long-term potentiation (LTP) in PFC slices of both control and FS animals is dependent on dopamine and that dopamine-dependent LTP is reduced by ketamine. We also found selective changes in ionotropic glutamate receptor subunit expression, phosphorylation, and localization at synaptic membranes induced by both acute stress and ketamine. Although more studies are needed to understand the effects of acute stress and ketamine on PFC glutamatergic plasticity, this first report suggests a restoring effect of acute ketamine, supporting the potential benefit of ketamine in limiting the impact of acute traumatic stress.

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