Abstract
<title>Abstract</title> <p> <bold>Introduction</bold> Object recognition memory (ORM) relies on two processes: familiarity, mediated by the perirhinal cortex (PRH), and recollection, supported by the hippocampus (HIP). These processes are recruited depending on memory strength: brief exploration forms weak traces relying on PRH familiarity, whereas extended exploration produces strong traces requiring HIP recollection. Noradrenaline (NA) modulates these mechanisms via β2-adrenergic receptors (β2-AR), influencing memory strength and consolidation. However, whether this modulation differs between sexes under conditions generating weak versus strong memory traces remains unknown. We examined how NA and β2-AR influence ORM in male and female mice under these conditions. <bold>Methods</bold> Swiss mice were tested in the Novel Object Recognition task using training durations of 1–10 minutes and delays of 24–48 hours. Atomoxetine (ATO) was used to increase NA levels, and ICI-118,551 (ICI) to block β2-AR. Neural activation was assessed via c-Fos immunohistochemistry in PRH and HIP. <bold>Results</bold> Females showed greater efficiency in object processing, requiring less exploration than males. Under weak training conditions, ATO facilitated the formation of long-term ORM in females but not in males, accompanied by increased PRH c-Fos expression without HIP involvement. β2-AR blockade impaired ORM acquisition only in females, with no significant changes in c-Fos. In males, performance depended on object dissimilarity; increased NA did not enhance ORM unless stimuli were highly distinct. <bold>Conclusions</bold> These findings reveal sex differences in noradrenergic modulation of ORM. In females, NA acting via β2-AR supports memory formation through PRH-dependent familiarity, emphasizing the importance of sex as a biological variable in research. </p>