Propranolol Administration During Morphine Addiction Attenuates Reinstatement of Drug-Aversive Memories Caused by Exposure to Stressful Stimuli

<b>Background/Objectives:</b> Situations previously paired with drug use can become conditioned stimuli (i.e., physical stress or psychosocial stress) that elicit intense craving and relapse, even after prolonged abstinence. Previous studies have shown that pharmacological disruption of reconsolidation after memory reactivation could be promising for reducing pathological fear and stress-related responses. For this reason, the aim of this research was to examine the role of β-AR in the retrieval of aversive memories through the potential of β-AR antagonism to mitigate the effects of exposure to stressful stimuli. <b>Methods:</b> This question was addressed using a model to assess the re-emergence of an aversive contextual memory induced by both physical stressors (restraint and tail-pinch) and psychosocial stress (social defeat) in morphine- or saline-treated mice previously subjected to a conditioned place aversion (CPA) paradigm, in which naloxone was administered to precipitate opioid withdrawal. To assess the effects of propranolol on aversive memories related to opioid addiction, the number of chamber crossings and the time spent in the naloxone-paired compartment were measured. <b>Results:</b> Our results showed that morphine-treated mice spent significantly less time in the naloxone-paired chamber than saline mice during the post-test and after exposure to stressful stimuli, than during the pre-test, showing an effect for aversive memories in addiction. In contrast, when propranolol was administered intraperitoneally 30 min before the exposure to both social and physical stress, the time spent enhanced significantly (<i>p</i> < 0.01), supporting a role for propranolol in addiction-related memories. <b>Conclusions:</b> These results suggest that propranolol could attenuate the aversive memories that may contribute to relapse to opioid addiction.