title: Histamine promotes rat motor performances by activation of H(2) receptors in the cerebellar fastigial nucleus.
abstract: The cerebellar fastigial nucleus (FN), together with the interpositus nucleus (IN), constitutes the two final output nuclei of the spinocerebellum and plays an important role in body and limb movements. Previous studies have revealed a direct histaminergic projection from the hypothalamus to the cerebellar nuclei and an excitatory effect of histamine on the IN neurons. However, role of hypothalamic histaminergic projection in the FN has been still little known. Here we show that histamine elicited the FN neurons of rats a concentration-dependent excitatory response in vitro. The histamine-induced excitation on FN neurons was mediated by postsynaptic histamine H2 rather than H1 receptors. In behavioral tests, microinjection of histamine into bilateral FNs remarkably improved motor performances of rats on both accelerating rota-rod and balance beam. Selective H2 receptor antagonist ranitidine considerably declined those motor performances and selective H2 receptor agonist dimaprit mimicked the facilitation effect of histamine on the movements. But selective H1 receptor antagonist triprolidine and agonist 2-pyridylethylamine had no effect. Furthermore, microinjection of histamine into bilateral FNs narrowed stride width of footprint but did not influence wire suspension, whereas microinjection of histamine into bilateral INs increased stride length and promoted suspension. These results demonstrate that histamine enhances rat motor balance and coordination through modulation of both proximal and distal muscles by activation of histamine H2 receptors in the cerebellar FN and IN, and suggest that the hypothalamocerebellar histaminergic projections may modulate the final outputs of the spinocerebellum and participate in the cerebellum-mediated motor control.
authors.affiliation: Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, Mailbox 426, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
authors.forename: Ye-Cheng
authors.initials: YC
authors.lastname: He
authors.forename: Guan-Yi
authors.initials: GY
authors.lastname: Wu
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Biao
authors.initials: B
authors.lastname: Tang
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.forename: Jing-Ning
authors.initials: JN
authors.lastname: Zhu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002529:Cerebellar Nuclei / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D018494:Histamine Agents / Q000494:pharmacology*; D017442:Histamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*
chemical_list: D018494:Histamine Agents; D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine