Yassine Bentefour1, Mohamed Bennis1, René Garcia2, Saadia Ba-M'hamed1. 1. Laboratoire de Pharmacologie, Neurobiologie et Comportement, Centre National de la Recherche Scientifique et Technique, URAC 37, Université Cadi Ayyad, Marrakech, Morocco. 2. Institut de Neurosciences de la Timone, UMR7289, Aix-Marseille Université & Centre National de la Recherche Scientifique, 13385 Marseille, France. Electronic address: rene.garcia@unice.fr.
Abstract
BACKGROUND: We have previously demonstrated, in mice, that antidepressant treatment can prevent relapse of PTSD-like behaviors (avoidance, hyperarousal, and anxiety) through increased activation in the infralimbic cortex (IL) of the medial prefrontal cortex. OBJECTIVE: Here, we examined whether direct high-frequency stimulation (HFS) of the IL, provoking its heightened activation (i.e., long-term potentiation, LTP), would also prevent the return of PTSD-like symptoms. METHODS: A 1.5-mA foot-shock was used to generate PTSD-like symptoms in Swiss mice. In Experiment 1, local field potentials were recorded in the IL to test whether normal IL LTP can be induced after the suppression of PTSD-like symptoms. In Experiment 2, IL HFS was applied after symptom suppression, but prior to the provocation of relapse, to test HFS effect on symptom return. RESULTS: We observed that PTSD-like state was associated with impairment in IL HFS-induced IL LTP. However, IL LTP induction was near normal when PTSD-like symptoms were suppressed. We then found that IL HFS, applied after symptom suppression, prevented symptom return. CONCLUSIONS: Increased activation of the IL may be a key mechanism preventing PTSD relapse. Prefrontal cortex deep brain stimulation may, therefore, be relevant for preventing PTSD symptom return in remitted high-risk patients.
BACKGROUND: We have previously demonstrated, in mice, that antidepressant treatment can prevent relapse of PTSD-like behaviors (avoidance, hyperarousal, and anxiety) through increased activation in the infralimbic cortex (IL) of the medial prefrontal cortex. OBJECTIVE: Here, we examined whether direct high-frequency stimulation (HFS) of the IL, provoking its heightened activation (i.e., long-term potentiation, LTP), would also prevent the return of PTSD-like symptoms. METHODS: A 1.5-mA foot-shock was used to generate PTSD-like symptoms in Swiss mice. In Experiment 1, local field potentials were recorded in the IL to test whether normal IL LTP can be induced after the suppression of PTSD-like symptoms. In Experiment 2, IL HFS was applied after symptom suppression, but prior to the provocation of relapse, to test HFS effect on symptom return. RESULTS: We observed that PTSD-like state was associated with impairment in IL HFS-induced IL LTP. However, IL LTP induction was near normal when PTSD-like symptoms were suppressed. We then found that IL HFS, applied after symptom suppression, prevented symptom return. CONCLUSIONS: Increased activation of the IL may be a key mechanism preventing PTSD relapse. Prefrontal cortex deep brain stimulation may, therefore, be relevant for preventing PTSD symptom return in remitted high-risk patients.