Propranolol can induce PTSD‐like memory impairments in rats

Abstract

IntroductionOne hallmark symptom of post‐traumatic stress disorder (PTSD) is an inability to restrict fear responses to the appropriate predictor. An infusion of glucocorticoids (GCs) after a high‐intensity shock has been shown to induce PTSD‐like memory impairments. In addition to GCs, noradrenergic signalling is also recognized as a key biomarker underlying PTSD symptomatology.MethodsTo explore the role of the noradrenergic system in PTSD‐like memory impairments, in this study, various doses of the β‐adrenoceptor antagonist propranolol were systemically or bilaterally injected into the dorsal hippocampus immediately after unpaired cue‐shock contextual fear conditioning, and then the rats were tested 24 h later.ResultsInterestingly, we found that only low‐dose propranolol could induce PTSD‐like memory impairments, as rats showed reduced freezing to the correct predictor and generalized fear responses to the safe cues, accompanied by increased NE levels in the hippocampus and altered neural activity within the frontal‐subcortical circuit.ConclusionThese findings demonstrate that the noradrenergic system is involved in regulating the consolidation of contextual fear memory and that propranolol can dose‐dependently induce PTSD‐like memory impairments.

Norepinephrine Induces PTSD-Like Memory Impairments via Regulation of the β-Adrenoceptor-cAMP/PKA and CaMK II/PKC Systems in the Basolateral Amygdala

“…Atsak et al ( 2012 ) indicated that post-training NE infusions into the dorsal hippocampus during retention of auditory fear conditioning has no significant effect on fear response. Our previous work (Zhu et al, 2018 ) suggested that intra-hippocampus infusion of propranolol, not NE, dose-dependently induced PTSD-like memory impairments. In addition, the PTSD-like memory impairment model used in this study can be regarded as the impairment of memory accuracy.…”

“…Evidence, including anatomical (Pikkarainen et al, 1999 ), behavioral (Roozendaal, 2000 ; Roozendaal et al, 2006c ; McReynolds et al, 2010 , 2014 ), electrophysiological (Akirav and Richter-Levin, 1999 ; Almaguer-Melian et al, 2003 ; Vouimba and Richter-Levin, 2013 ), and optogenetic data (Nabavi et al, 2014 ; Redondo et al, 2014 ; Tanaka et al, 2014 ; Rei et al, 2015 ), has shown that the amygdala modulates hippocampal memory storage. One of our recent studies found that an intrahippocampal infusion of propranolol dose-dependently induced PTSD-like memory impairments, demonstrating that the NE system in the hippocampus was involved in the formation of PTSD-like memory impairment (Zhu et al, 2018 ). However, whether NE within the BLA is a key factor in PTSD-like memory impairments remains unclear.…”

Rethinking avoidance

“…The enhancing effect of acute stress on the generalization of fear (i.e., US expectancies) described in Chapter 3 align well with previous studies that observed an acute stress or cortisol effect on fear generalization in humans (e.g., and animals (e.g., Bender et al, 2018;Kaouane et al, 2012;Kolodziejczyk & Fendt, 2020;Lesuis et al, 2021;Liu et al, 2019;Ren et al, 2022;Zhu et al, 2018). However, a recent study failed to find an effect of acute stress on fear generalization in healthy individuals (Kausche, Zerbes, Kampermann, Büchel, et al, 2021).…”

Phencyclidine and Scopolamine for Modeling Amnesia in Rodents: Direct Comparison with the Use of Barnes Maze Test and Contextual Fear Conditioning Test in Mice

“…Fear conditioning is strongly associated with some psychiatric disorders like phobias, or post-traumatic stress disorder (PTSD). Recently, a strong link between PTSD and memory impairments has been shown by Zhu and colleagues (Zhu et al 2017 ). These authors investigated memory impairments in PTSD-exposed rats, and they observed significant changes in prefrontal cortex, hippocampus, and amygdala of stressed animals.…”