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Lithium and tamoxifen modulate cellular plasticity cascades in animal model of mania.
- Source :
-
Journal of psychopharmacology (Oxford, England) [J Psychopharmacol] 2012 Dec; Vol. 26 (12), pp. 1594-604. Date of Electronic Publication: 2012 Oct 17. - Publication Year :
- 2012
-
Abstract
- Lithium (Li) is the main mood stabilizer and acts on multiple biochemical targets, leading to neuronal plasticity. Several clinical studies have shown that tamoxifen (TMX) - a protein kinase C (PKC) inhibitor - has been effective in treating acute mania. The present study aims to evaluate the effects of TMX on biochemical targets of Li, such as glycogen synthase kinase-3β (GSK-3β), PKC, PKA, CREB, BDNF and NGF, in the brain of rats subjected to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were treated with d-AMPH (2mg/kg, once a day) or saline (Sal; NaCl 0.9%, w/v), Li (47.5 mg/kg, intraperitoneally (i.p.), twice a day) or TMX (1 mg/kg i.p., twice a day) or Sal in protocols of reversion and prevention treatment. Locomotor behavior was assessed using the open-field task, and protein levels were measured by immunoblot. Li and TMX reversed and prevented d-AMPH-induced hyperactivity. Western blot showed that d-AMPH significantly increased GSK-3 and PKC levels, and decreased pGSK-3, PKA, NGF, BDNF and CREB levels in the structures analyzed. Li and TMX were able to prevent and reverse these changes induced by d-AMPH in most structures evaluated. The present study demonstrated that the PKC inhibitor modulates the alterations in the behavior, neurotrophic and apoptosis pathway induced by d-AMPH, reinforcing the need for more studies of PKC as a possible target for treatment of bipolar disorder.
- Subjects :
- Animals
Apoptosis drug effects
Behavior, Animal drug effects
Blotting, Western
Dextroamphetamine toxicity
Disease Models, Animal
Injections, Intraperitoneal
Male
Motor Activity drug effects
Neuronal Plasticity drug effects
Protein Kinase C drug effects
Protein Kinase C metabolism
Rats
Rats, Wistar
Antimanic Agents pharmacology
Bipolar Disorder drug therapy
Lithium pharmacology
Tamoxifen pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1461-7285
- Volume :
- 26
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of psychopharmacology (Oxford, England)
- Publication Type :
- Academic Journal
- Accession number :
- 23076832
- Full Text :
- https://doi.org/10.1177/0269881112463124