title: Myricitrin, a nitric oxide and protein kinase C inhibitor, exerts antipsychotic-like effects in animal models.
abstract: Myricitrin is a nitric oxide (NO) and protein kinase C (PKC) inhibitor that has central nervous system activity, including anxiolytic-like action. Nitric oxide inhibitors blocked the behavioral effects of apomorphine, suggesting an antipsychotic-like effect. Furthermore, PKC inhibition reduced psychotic symptoms in acute mania patients and blocked amphetamine-induced hyperlocomotion, suggesting a potential antipsychotic-like effect. The present study evaluated the effects of myricitrin in animal models that assess antipsychotic-like effects (apomorphine-induced stereotypy and climbing and the paw test) and extrapyramidal side effects (catalepsy test and paw test). Olanzapine was used as a positive control. 7-Nitroindazole (7-NI), a NOS inhibitor, and l-arginine, a NO precursor, were used to evaluate nitrergic modulation, and tamoxifen was used to test the effect of PKC inhibition. In mice, myricitrin dose-dependently and olanzapine blocked the stereotypy and climbing induced by apomorphine at doses that did not induce catalepsy. 7-Nitroindazole also blocked apomorphine-induced stereotypy and climbing, which were reversed by l-arginine pretreatment. l-arginine only attenuated the effects of myricitrin on apomorphine's effects. Tamoxifen also blocked apomorphine-induced stereotypy and climbing. In the paw test in rats, myricitrin and olanzapine increased hindlimb retraction time at doses that did not affect forelimb reaction time, whereas haloperidol affected both parameters at the same dose. Myricitrin did not induce catalepsy in the bar test. Tamoxifen did not affect hindlimb retraction time or forelimb retraction time, whereas 7-NI significantly increased hindlimb reaction time. Thus, myricitrin exhibited an antipsychotic-like profile at doses that did not induce catalepsy, and this effect may be related to nitrergic action.
authors.affiliation: Laboratório de Fisiologia e Farmacologia do Sistema Nervoso Central, Departamento de Farmacologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, 81540-990, Curitiba, PR, Brazil. mp.deutch@yahoo.com.br
authors.forename: M
authors.initials: M
authors.lastname: Pereira
authors.forename: I P
authors.initials: IP
authors.lastname: Siba
authors.forename: L R
authors.initials: LR
authors.lastname: Chioca
authors.forename: D
authors.initials: D
authors.lastname: Correia
authors.forename: M A B F
authors.initials: MA
authors.lastname: Vital
authors.forename: M G
authors.initials: MG
authors.lastname: Pizzolatti
authors.forename: A R S
authors.initials: AR
authors.lastname: Santos
authors.forename: R
authors.initials: R
authors.lastname: Andreatini
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001058:Apomorphine / Q000494:pharmacology / Q000627:therapeutic use; D001120:Arginine / Q000494:pharmacology / Q000627:therapeutic use; D002375:Catalepsy / Q000139:chemically induced; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D007191:Indazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D008517:Phytotherapy; D018515:Plant Leaves; D028321:Plant Preparations / Q000494:pharmacology* / Q000627:therapeutic use; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D027842:Syzygium; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D005419:Flavonoids; D007191:Indazoles; D028321:Plant Preparations; D013629:Tamoxifen; D009569:Nitric Oxide; C008577:myricitrin; D001120:Arginine; D011493:Protein Kinase C; D001058:Apomorphine; C080122:7-nitroindazole