Synthetic retinoid Am80 results in improved exploratory and emotional behavior in the P8 substrain of senescence-accelerated mice

Abstract

Am80 is a synthetic retinoid that has been used clinically for patients with acute promyelocytic leukemia and has been reported to affect the brain and its neurons. We investigated the influence of Am80 on anti-anxiety-like behavior, which is a characteristic of age-associated emotional disorder, in the P8 strain of senescence-accelerated mice (SAMP8). Am80 at a concentration of 2 mg/kg/day was administered to the mice in their feed for 1.5 months. In open-field and hole-board tests, the number of ambulation, rearing, and head dipping actions, as well as the distance moved were significantly decreased in Am80-treated SAMP8 compared with untreated SAMP8. In the light/dark box test, the latencies for the first exit were significantly increased in the Am80-treated SAMP8 compared with the untreated SAMP8. Immunohistochemical analysis revealed that the area of serotonin transporter-positive immunoreactivity in the coronal sections of the forebrain of the Am80-treated SAMP8 was increased compared with the untreated SAMP8. Furthermore, the metabolic turnovers of serotonin and dopamine were increased in the amygdalae of the SAMP8 by Am80 treatment. Thus, in the present study, Am80 was found to improve exploratory and emotional behavior in SAMP8, suggesting that Am80 regulates monoamines directly or indirectly in this senescence-accelerated model.