Influência do sistema histaminérgico cerebelar no comportamento locomotor e ansiedade de camundongos

Abstract

The cerebellum is an important structure of the central nervous system with participation in motor and non-motor functions. The histaminergic system has a major role on the cerebellar neuronal circuit, but its function is not fully understood. The histamine can act through four types of receptors: H1, H2, H3 and H4. There are few studies about the role of the cerebellar histaminergic system on motor and non-motor functions. Thus, the main objective of this study is to investigate the effects of the intravermis cerebellar microinjections of histaminergic compounds, proposing a possible interaction of this system and the cerebellum on the modulation of motor and non-motor functions. The study was composed by five experiments, to evaluate the effects of Histamine (experiment 1), H1 receptor antagonist Chlorpheniramine (experiment 2), H2 receptor antagonist Ranitidine (experiment 3), H3 receptor antagonist Thioperamide (experiment 4) and H4 receptor agonist VUF-8430 (experiment 5) on the locomotor and anxiety-like behaviors in mice exposed to the open field test. A stereotaxic surgery was performed, and a guide canulla was implanted into the cerebellar vermis of mice weighing between 25 – 35g. Three days after surgery, the animals received the microinjection and were exposed to the open field behavioral test. The number of crossed quadrants, number of rearings and time in the central area was measured. The histological analysis confirmed the place of the microinjection. The statistical analysis was composed by one way ANOVA, follow by Duncan’s post hoc when appropriate. The results indicate that the higher doses of chlorpheniramine and VUF has an anxiogenic effect associated to increase of the locomotor and exploratory behaviors of mice, indicating a possible modulation of the cerebellar histaminergic system in these functions, through H1 and H4 receptors.