title: [Regulation of dopaminergic neuronal activity by heart-type fatty acid binding protein in the brain].
abstract: Haloperidol as a potent dopamine D2 receptor (D2R) antagonist was a major tranquilizer to treat schizophrenia patients. However, the D2R blocking action in dorsal striatum is thought to cause extrapyramidal symptoms as adverse effects. However, the pathophysiological mechanism underlying extrapramidal symptoms induced by chronic treatment of haloperidol remains unclear. We recently found that lacking of heart-type fatty acid binding protein (H-FABP) in the brain aggravate catalepsy behavior induced by haloperidol. Here, we examined neuronal mechanism of augmentation of haloperidol-induced catalepsy in H-FABP null mice. Notably, catalepsy induced by haloperidol, a D2 antagonist, is augmented, whereas catalepsy induced by SCH23390, a D1 antagonist, was not affected in H-FABP null mice. Interestingly, haloperidol-induced acetylcholine (ACh) release in the dorsal striatum was markedly enhanced in H-FABP null mice compared to wild mice. We also defined the co-localization of D2R with H-FABP in the ACh interneurons in the striatum. Taken together, H-FABP regulates dopaminergic neuronal activity through interaction with D2R in rodent brain. The increased ACh release in the striatum accounts for haloperidol-induced catalepsy.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba-ku, Sendai, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Norifumi
authors.initials: N
authors.lastname: Shioda
authors.forename: Yuji
authors.initials: Y
authors.lastname: Owada
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced; D001921:Brain / Q000378:metabolism*; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000009:adverse effects / Q000494:pharmacology; D050556:Fatty Acid-Binding Proteins / Q000502:physiology*; D006220:Haloperidol / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009474:Neurons / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology
chemical_list: D018492:Dopamine Antagonists; D050556:Fatty Acid-Binding Proteins; D017448:Receptors, Dopamine D2; D006220:Haloperidol; D000109:Acetylcholine; D004298:Dopamine