Myricitrin, a nitric oxide and protein kinase C inhibitor, exerts antipsychotic-like effects in animal models

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 35; no. 7; pp. 1636 - 1644
• Main Authors: Pereira, M., Siba, I.P., Chioca, L.R., Correia, D., Vital, M.A.B.F., Pizzolatti, M.G., Santos, A.R.S., Andreatini, R.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 15.08.2011; Elsevier
• Subjects: Animals; Antipsychotic; Antipsychotic Agents - pharmacology; Antipsychotic Agents - therapeutic use; Apomorphine - pharmacology; Apomorphine - therapeutic use; Arginine - pharmacology; Arginine - therapeutic use; Biological and medical sciences; Catalepsy; Catalepsy - chemically induced; Climbing; Disease Models, Animal; Dopamine Agonists - pharmacology; Dopamine Agonists - therapeutic use; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Flavonoids - pharmacology; Flavonoids - therapeutic use; Indazoles - antagonists & inhibitors; Indazoles - pharmacology; Indazoles - therapeutic use; Male; Medical sciences; Mice; Motor Activity - drug effects; Neuropharmacology; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - physiology; Pharmacology. Drug treatments; Phytotherapy; Plant Leaves; Plant Preparations - pharmacology; Plant Preparations - therapeutic use; Protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - physiology; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Psychotic Disorders - drug therapy; Psychotic Disorders - physiopathology; Rats; Rats, Wistar; Stereotyped Behavior - drug effects; Stereotyped Behavior - physiology; Stereotypy; Syzygium; Tamoxifen - pharmacology; Tamoxifen - therapeutic use; NO; L-NAME; Protein kinase C; L-NOARG; Catalepsy; Climbing; 7-NI; FRT; PKC; HRT; SNAP; Glu; NOS; DAT; Nitric oxide; nNOS; NMDA; Antipsychotic; DA; Stereotypy; Animal model; Enzyme; Neuroleptic; Psychotropic; Transferases; Pharmacotherapy; Treatment; Inhibitor
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2011.06.002

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. [Display omitted] ► Myricitrin shows antipsychotic-like effects in animal models. ► The myricitrin and 7-NI antipsychotic-like effects were reverted by l-arginine. ► The results suggest a nitrinergic mediation for myricitrin antipsychotic-like effect.