title: Antimanic-like effect of tamoxifen is not reproduced by acute or chronic administration of medroxyprogesterone or clomiphene.
abstract: Tamoxifen, a protein kinase C (PKC) inhibitor and antiestrogenic drug, has clinical antimanic effects and blocks psychostimulant-induced hyperlocomotion. Medroxyprogesterone (MPA), which has antiestrogenic effects, also exerts some clinical benefits in female manic patients and partially blocks amphetamine-induced hyperlocomotion, indicating that the antiestrogenic effect of tamoxifen could contribute to its antimanic effect. The present study evaluated the effect of acute and chronic (21 day) treatment of two antiestrogenic drugs, MPA and clomiphene (an estrogenic receptor antagonist), on methylphenidate (MPH, 5.0mg/kg)-induced hyperlocomotion in mice, an animal model of mania. Acute and chronic tamoxifen administration was used as a positive control. Acute and chronic tamoxifen (1.0mg/kg) administration blocked MPH-induced hyperlocomotion. Acute and chronic MPA (acute: 3.0 or 6.0mg/kg; chronic: 3.0mg/kg) and clomiphene (acute: 1.5 or 3.0mg/kg; chronic: 1.5mg/kg) treatment did not alter MPH-induced hyperlocomotion. These results indicate that tamoxifen exerts antimanic-like effects, and reduced estrogenic activity does not have antimanic-like effects in this psychostimulant-induced hyperlocomotion model. Therefore, the antiestrogenic effect of tamoxifen likely does not contribute to its antimanic effect, which may instead be related to its effect on PKC activity. Therefore, PKC inhibition may be associated with the antimanic effect of mood stabilizers.
authors.affiliation: Department of Pharmacology, Federal University of Paraná (UFPR), Curitiba, PR 81540-990, Brazil.
authors.forename: Marcela
authors.initials: M
authors.lastname: Pereira
authors.forename: Bruno Jacson
authors.initials: BJ
authors.lastname: Martynhak
authors.forename: Irinéia Paulina
authors.initials: IP
authors.lastname: Baretta
authors.forename: Diego
authors.initials: D
authors.lastname: Correia
authors.forename: Isadora Pozzetti
authors.initials: IP
authors.lastname: Siba
authors.forename: Roberto
authors.initials: R
authors.lastname: Andreatini
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002996:Clomiphene / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D008297:Male; D008525:Medroxyprogesterone / Q000494:pharmacology*; D008774:Methylphenidate / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D002996:Clomiphene; D008774:Methylphenidate; D011493:Protein Kinase C; D008525:Medroxyprogesterone