Efeito do lítio na modulação de comportamento similar à mania induzido por variações de fotoperíodo

Abstract

Bipolar disorder (BD) is a chronic mood disorder, affecting approximately 2-3% of the global population. Mania is a cardinal feature of BD and is characterized by symptoms as impulsivity and hyperactivity. Epidemiological studies show higher occurrence of hospitalizations for manic episodes in periods of accentuated increments in day length, or photoperiod. Consistently, preliminary studies performed by our group indicate that a gradual increase of the photoperiod is associated with a mania-like behavior in C57BL/6 mice. The hypothesis is that gradual variations in photoperiod modulate the circadian rhythms in brain regions associated with mood disorders. Lithium (Li) is a mood stabilizer used in the treatment of bipolar disorders in humans with antimanic and antidepressant properties. Furthermore, Li treatment modulates mood-related behavior in rodents. The aim of this work is to validate the photoperiodic induced mania-like animal model by pharmacologically testing lithium as a mood stabilizer. The animals that were used in the present study are male C57BL/6J mice, distributed into the three groups: (1) EP (Equatorial Photoperiod), (2) TP (Transitional Photoperiod) and (3) TP-Li. The animals of Eq group were exposed to a light/dark regime (CE) 12h:12h. The TP group consists of mice exposed to a regime of gradual photoperiodic variations (30min at the beginning and 30 min at the end of light phase/day) from 08h:16h CE to a 16h:8h CE, with food and water ad libitum. The TP-Li group animals were submitted to the same photoperiodic protocol but Lithium Chloride (0,6g/L) was administered in drinking water for eight days, from the first day to the last day of the TP regime. Elevated Pluz Maze, Open Field Test, Forced Swimming Test and Hole Board were performed to evaluate hyperactivity, anxiety, risk-taking, depression and mania. The TP -Li group showed a decrease in risk exposure, exploratory behavior and hyperlocomotion when compared to the TP and similar to the control group. The findings demonstrate that lithium administration prevents the mania-like behavior observed in the experimental condition. This study contributes to the establishment of a new model of bipolar disorder based on the manipulation of ambient light.