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

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.

Neonatal phencyclidine treatment in mice induces behavioral, histological and neurochemical abnormalities in adulthood.

We investigated the involvement of glutamic acid in neural development by injecting phencyclidine (PCP) into neonatal ICR mice. Neonatal mice were injected with PCP at 10 mg/kg or saline on postnatal days 7, 9 and 11, and their behavioral, anatomical and neurochemical changes were analyzed in adulthood. PCP-treated mice exhibited an increase in PCP-induced hyperactivity and impairments of spatial working memory and social interaction behavior. The impairment of social interaction behavior was significantly reversed by administration of clozapine, D-cycloserine, flumazenil, or SHC50911, a gamma-aminobutyrate B (GABA(B)) receptor antagonist. A decrease in the number of parvalbumin-positive cells and spine density in the frontal cortex, nucleus accumbens and hippocampus were evident in the brains of PCP-treated mice. Measurement of brain monoamine and their metabolite contents in adulthood indicated brain area-dependent and neurotransmitter-specific changes in monoamine metabolism. These findings suggest that neonatal treatment with PCP in mice leads to enhanced sensitivity to PCP and impairment of spatial working memory and social interaction behaviors in adulthood, which may be associated with reduced spine density and GABAergic interneurons and changes in monoamine metabolism. Furthermore, pharmacologic experiments suggest the potential applicability of neonatally PCP-treated mice as a useful animal model for new antipsychotic drug screening.