title: Protein kinase C regulates mood-related behaviors and adult hippocampal cell proliferation in rats.
abstract: The neurobiological mechanisms underlying the pathophysiology and therapeutics of bipolar disorder are still unknown. In recent years, protein kinase C (PKC) has emerged as a potential key player in mania. To further investigate the role of this signaling system in mood regulation, we examined the effects of PKC modulators in behavioral tests modeling several facets of bipolar disorder and in adult hippocampal cell proliferation in rats. Our results showed that a single injection of the PKC inhibitors tamoxifen (80 mg/kg, i.p.) and chelerythrine (3 mg/kg, s.c.) attenuated amphetamine-induced hyperlocomotion and decreased risk-taking behavior, supporting the efficacy of PKC blockade in acute mania. Moreover, chronic exposure to tamoxifen (10 mg/kg/day, i.p., for 14 days) or chelerythrine (0.3 mg/kg/day, s.c., for 14 days) caused depressive-like behavior in the forced swim test, and resulted in a reduction of cell proliferation in the dentate gyrus of the hippocampus. Finally, we showed that, contrary to the PKC inhibitors, the PKC activator phorbol 12-myristate 13-acetate (PMA) enhanced risk-taking behavior and induced an antidepressant-like effect. Taken together, these findings support the involvement of PKC in regulating opposite facets of bipolar disorder, and emphasize a major role for PKC in this disease.
authors.affiliation: Université de Lyon, F-69373, Lyon, France.
authors.forename: Erika
authors.initials: E
authors.lastname: Abrial
authors.forename: Adeline
authors.initials: A
authors.lastname: Etievant
authors.forename: Cécile
authors.initials: C
authors.lastname: Bétry
authors.forename: Hélène
authors.initials: H
authors.lastname: Scarna
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lucas
authors.forename: Nasser
authors.initials: N
authors.lastname: Haddjeri
authors.forename: Laura
authors.initials: L
authors.lastname: Lambás-Señas
mesh_terms: D000339:Affect / Q000502:physiology*; D000818:Animals; D000963:Antimetabolites; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology*; D001714:Bipolar Disorder / Q000523:psychology; D001973:Bromodeoxyuridine; D002452:Cell Count; D049109:Cell Proliferation; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D003863:Depression / Q000523:psychology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D012309:Risk-Taking; D015398:Signal Transduction / Q000502:physiology; D013238:Stereotaxic Techniques; D013550:Swimming / Q000523:psychology
chemical_list: D000963:Antimetabolites; D000697:Central Nervous System Stimulants; D047428:Protein Kinase Inhibitors; D011493:Protein Kinase C; D001973:Bromodeoxyuridine; D003913:Dextroamphetamine