RATIONALE: In the context of bipolar disorder (BPD) research it was demonstrated that administration of the structurally dissimilar mood stabilizers lithium and valproate produced a striking reduction in protein kinase C (PKC) in rat brain. In a small clinical study, tamoxifen (a PKC inhibitor) had antimanic efficacy. However, both lithium and valproate exert many biochemical changes and attribution of therapeutic relevance to any molecular findings needs to be based on linking them to behavioral effects. OBJECTIVES: The present study was designed to explore such relationship by studying the effects of PKC inhibition in amphetamine-induced behavioral animal models of mania and changes in GAP-43. METHODS: The effects of two daily tamoxifen (1 mg/kg) i.p. injections on acute or chronic (7 injections) amphetamine (0.5 mg/kg) -induced behaviors and GAP-43 phosphorylation were tested. RESULTS: The study demonstrates that tamoxifen significantly reduced amphetamine-induced hyperactivity in a large open field without affecting spontaneous activity levels and normalized amphetamine-induced increase in visits to the center of an open field (representing risk-taking behavior). Tamoxifen also attenuated amphetamine-induced phosphorylation of GAP-43, a result that is consistent with the behavioral findings. CONCLUSIONS: These results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD. These findings may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder. (c) 2007 S. Karger AG, Basel.
RATIONALE: In the context of bipolar disorder (BPD) research it was demonstrated that administration of the structurally dissimilar mood stabilizers lithium and valproate produced a striking reduction in protein kinase C (PKC) in rat brain. In a small clinical study, tamoxifen (a PKC inhibitor) had antimanic efficacy. However, both lithium and valproate exert many biochemical changes and attribution of therapeutic relevance to any molecular findings needs to be based on linking them to behavioral effects. OBJECTIVES: The present study was designed to explore such relationship by studying the effects of PKC inhibition in amphetamine-induced behavioral animal models of mania and changes in GAP-43. METHODS: The effects of two daily tamoxifen (1 mg/kg) i.p. injections on acute or chronic (7 injections) amphetamine (0.5 mg/kg) -induced behaviors and GAP-43 phosphorylation were tested. RESULTS: The study demonstrates that tamoxifen significantly reduced amphetamine-induced hyperactivity in a large open field without affecting spontaneous activity levels and normalized amphetamine-induced increase in visits to the center of an open field (representing risk-taking behavior). Tamoxifen also attenuated amphetamine-induced phosphorylation of GAP-43, a result that is consistent with the behavioral findings. CONCLUSIONS: These results support the possibility that PKC signaling may play an important role in the pathophysiology and treatment of BPD. These findings may have direct clinical implications as they offer a new avenue for attempts to develop more specific drugs for the disorder. (c) 2007 S. Karger AG, Basel.
Authors: Gislaine T Rezin; Camila B Furlanetto; Giselli Scaini; Samira S Valvassori; Cinara L Gonçalves; Gabriela K Ferreira; Isabela C Jeremias; Wilson R Resende; Mariane R Cardoso; Roger B Varela; João Quevedo; Emilio L Streck Journal: Mol Neurobiol Date: 2013-10-15 Impact factor: 5.590
Authors: Rose Mary Carvalho Pinheiro; Maria Noêmia Martins de Lima; Gabriel Rodrigo Fries; Vanessa Athaíde Garcia; Juliana Presti-Torres; Luis Henrique Hallmenschlager; Luisa Azambuja Alcalde; Rafael Roesler; Monica Levy Andersen; João Quevedo; Flávio Kapczinski; Nadja Schröder Journal: J Neural Transm (Vienna) Date: 2012-01-05 Impact factor: 3.575