<p>Dysregulation of normal reward processing via psychological stress contributes to the development of psychiatric disorders. Estrogen is involved in reward processing in females, but this effect has not been well&#xa0;studied in males despite the abundant conversion of androgens to estrogens in the male brain. Here, we used a combination of genetic deletions, behavioral assays, pharmacology, circuit dissection, electrophysiology, in vivo fiber photometry, and optogenetics/chemogenetics to determine the role of the most prevalent and potent estrogen, 17β-estradiol, in male stress-induced reward processing dysfunction. We found that absence of estrogen receptor (ER) β renders male but not female mice susceptible to stress-induced maladaptive reward-processing behaviors. We demonstrated that activation of ERβ-projecting neurons from the basolateral amygdala to nucleus accumbens induced rewarding effects in male, but not female mice. Moreover, we show that the activity of ERβ-expressing neurons projecting from the basolateral amygdala to nucleus accumbens is reduced in hypogonadal male mice subjected to stress, while activation of this circuit reverses stress-induced maladaptive reward processing behaviors and inhibition induces stress susceptibility. We identified that absence of estradiol, but not testosterone per se, underlies susceptibility to stress-mediated dysfunction of rewarding behaviors and that brain-selective delivery of estradiol and intra-basolateral amygdala administration of an ERβ-specific agonist prevent maladaptive reward-processing behaviors in hypogonadal male mice. These findings delineate an estrogen-based mechanism underlying stress susceptibility and provide a novel therapeutic strategy for the treatment of reward-related disorders associated with hypogonadal conditions.</p>