This study elucidated the potential antidepressant-like effect of prolonged RoprenA (R) administration (8.6 mg/kg, orally, once daily for 28 days) using a beta-amyloid (25-35) rat model of Alzheimer's disease following gonadectomy. The experimental model was created by intracerebroventricular injection of beta-amyloid (25-35) into gonadectomized (GDX) rats and GDX rats with testosterone propionate (TP, 0.5 mg/kg, subcutaneous, once daily, 28 days) supplementation. RoprenA (R) was administered to the GDX rats and GDX rats treated with TP. Depression-like behavior was assessed in the forced swimming test, and the spontaneous locomotor activity was assessed using the open-field test. The corticosterone and testosterone levels in the blood serum before and after FST were measured in all experimental groups. Treatment with RoprenA (R) significantly decreased the immobility time of GDX rats with beta-amyloid (25-35) in the forced swimming test. Coadministration of RoprenA (R) with TP exerted a markedly synergistic antidepressant-like effect in the GDX rats with beta-amyloid (25-35 on the same model of depression-like behavior testing. RoprenA (R) administered alone or together with TP significantly enhanced crossing, frequency of rearing, and grooming of the GDX rats with beta-amyloid (25-35) in the open-field test. Moreover, RoprenA (R) administered alone or together with TP significantly decreased the elevated corticosterone levels in the blood serum of GDX rats with beta-amyloid (25-35) following the forced swimming test. These results indicate that RoprenA (R) has a marked antidepressant-like effect in the experimental model of Alzheimer's disease in male rats with altered levels of androgens.