Associative memory can be rendered malleable by a reminder. Blocking the ensuing reconsolidation process is suggested as a therapeutic target for unwanted aversive memories. Matrix metalloproteinase-9 (MMP-9) is required for structural synapse remodeling involved in memory consolidation. Inhibiting MMP-9 with doxycycline is suggested to attenuate human threat conditioning. Here, we investigated whether MMP-9 inhibition also interferes with threat memory reconsolidation. Male and female human participants (N = 78) learned the association between two visual conditioned stimuli (CS+) and a 50% chance of an unconditioned nociceptive stimulus (US), and between CS− and the absence of US. On day 7, one CS+ was reminded without reinforcement 3.5 h after ingesting either 200 mg of doxycycline or placebo. On day 14, retention of CS memory was assessed under extinction by fear-potentiated startle. Contrary to our expectations, we observed a greater CS+/CS− difference in participants who were reminded under doxycycline compared with placebo. Participants who were reminded under placebo showed extinction learning during the retention test, which was not observed in the doxycycline group. There was no difference between the reminded and the nonreminded CS+ in either group. In contrast, during relearning after the retention test, the CS+/CS− difference was more pronounced in the placebo group than in the doxycycline group. To summarize, a single dose of doxycycline before threat memory reminder appeared to have no specific impact on reconsolidation, but to globally impair extinction learning, and threat relearning, beyond drug clearance.SIGNIFICANCE STATEMENT Matrix metalloproteinase-9 inhibition appears to attenuate memory consolidation. It could also be a target for blocking reconsolidation. Here, we test this hypothesis in human threat conditioning. We find that doxycycline has no specific impact on a reminded cue, but confers a global reduction in extinction learning and threat learning beyond the clearance of the drug. This may point toward a more long-lasting impact of doxycycline treatment on memory plasticity.

IntroductionSuicide represents a major mental and public health issue. Elite athletes share certain individual and environmental characteristics that may increase their risk for mental illnesses, ultimately leading to suicide. This notion conflicts with the general perception of athletes, being the healthiest representatives of society.MethodsA comprehensive literature search was carried out through PubMed and Embase databases for relevant publications.ResultsRecent calls for investigating suicidality among athletes resulted in a considerable amount of literature providing some evidence regarding lower rates of suicide among professional and high‐performance athletes as well as similar incidence and prevalence of mental conditions, which are known as risk factors for suicide. Nevertheless, special attention is required in this population as predisposing and precipitating factors might differ from classical features of suicidality in the general population. Sports physicians, sports psychiatrists, and other mental health professionals in elite sports should be aware of early signs of affective disorders, risk of recreational drug abuse, misuse of performance‐enhancing medications, sport‐specific environmental stressors, serious physical injuries, and presence of physical or mental illness, all of which may increase suicidality. Traumatic brain injury (TBI) is with suicide with higher severity correlated with increased risk. Compared to active athletes, former athletes may have higher rates of suicide due to common life stressors occurring after sports retirement.ConclusionsThe findings suggest a multidisciplinary approach to suicidality in elite athletes, the main goal of which should be the reduction of suicide‐related morbidity and mortality. Further research is required to clarify the existing gaps in the current knowledge of the issue. While having lower rates of suicide, athletes share some similar (affective disorders, drug abuse, mental and physical illness) and unique factors (misuse of performance‐enhancing substances, sports‐related stressors, sports injuries, TBI) putting them at risk of suicide during active career and retirement.