Title : Histamine improves mice rota-rod performance through H1 and H2 receptors in the cerebellar vermis
The neural histaminergic system innervates the cerebellum, with high density of fibers in the vermis and flocculus. Experimental evidence indicates that cerebellum is involved in various non-motor as well as motor operations. However, the role of histaminergic system in these functions is not clear. Since our recent results have demonstrated the participation of the cerebellar histaminergic system in the consolidation of emotional memory, this study aims to investigate a possible interaction of this system in processing motor and non-motor function. First of all, we’ve conducted an experiment to investigate the dose-dependent effects of histamine, H1-receptor antagonist chlorpheniramine and H2-receptor antagonist ranitidine microinjected in the cerebellar vermis on motor performance and motor learning in mice. For this, we used Swiss albino mice (weighing 25-35g) and maintained in a thermoregulated environment. The drugs used were histamine (0.54nmol, 1.36nmol, 2.72nmol and 4.07nmol), chlorpheniramine or CPA (0.016 nmol, 0.052 nmol, 0.16 nmol), ranitidine (0.57 nmol, 2.85 nmol e 5.7 nmol) and saline 0.9%. After being anesthetised, a guide cannula was implanted into the cerebellar vermis following coordinates from the mouse brain atlas of Paxinos and Franklin. The protocol was divided in five steps, which were named habituation, microinjection, stage 1, stage 2, and stage 3. Twenty four hours later, the animals received a microinjection of saline or drugs. Five minutes later, the mice were submitted to stage 1, where they were placed in rota-rod and in the balance beam, each for 3 times, with 5 minutes of rest between each time. The protocol was repeated 4h later for stage 2 and repeated again 24h later for stage 3. Statistical analysis included the homogeneity test and multi-factor analysis of variance (ANOVA) followed by Duncan’s Multiple Range test. A p value of ≤0.05 was required for significance. The results showed a possible facilitation of histamine at the highest dose in the evaluation of learning and motor performance in the rota-rod. In addition, the results showed an impairment when tested at the 0.052 dose of CPA and at the lowest doses of ranitidine. This suggests that cerebellar histaminergic projections are involved in motor learning and make a modulating role in the cerebellar circuit to ensure that movements are performed efficiently.