Propranolol can induce PTSD-like memory impairments in rats

Introduction: One 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. Methods: To 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. Results: Interestingly, 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. Conclusion: These 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.