title: Calcium homeostasis and protein kinase/phosphatase balance participate in nicotine-induced memory improvement in passive avoidance task in mice.
abstract: Long-term potentiation (LTP) and long-term depression (LTD) depend on specific postsynaptic Ca2+/calmodulin concentration. LTP results from Ca2+influx through the activated NMDA receptors or voltage-gated calcium channels (VGCCs) and is linked with activation of protein kinases including mitogen-activated protein kinase (MAPK). Weaker synaptic stimulation, as a result of low Ca2+influx, leads to activation of Ca2+/calmodulin-dependent phosphatase (calcineurin - CaN) and triggers LTD. Interestingly, both memory formation and drug addiction share similar neuroplastic changes. Nicotine, which is one of the most common addictive drugs, manifests its memory effects through nicotinic acetylcholine receptors (nAChRs). Because nAChRs may also gate Ca2+, it is suggested that calcium signaling pathways are involved in nicotine-induced memory effects. Within the scope of the study was to evaluate the importance of calcium homeostasis and protein kinase/phosphatase balance in nicotine-induced short- and long-term memory effects. To assess memory function in mice passive avoidance test was used. The presented results confirm that acute nicotine (0.1mg/kg) improves short- and long-term memory. Pretreatment with L-type VGCC blockers (amlodipine, nicardipine verapamil) increased nicotine-induced memory improvement in the context of short- and long-term memory. Pretreatment with FK-506 (a potent CaN inhibitor) enhanced short- but not long-term memory effects of nicotine, while SL-327 (a selective MAPK/ERK kinase inhibitor) attenuated both nicotine-induced short- and long-term memory improvement. Acute nicotine enhances both types of memory via L-type VGCC blockade and via ERK1/2 activation. Only short- but not long-term memory enhancement induced by nicotine is dependent on CaN inhibition.
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland. Electronic address: agnieszka.michalak@umlub.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Michalak
authors.affiliation: Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4a Chodźki Street, 20-093 Lublin, Poland.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Biala
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D011930:Reaction Time / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D018722:Nicotinic Agonists; D011480:Protease Inhibitors; D009538:Nicotine; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases
keywords: FK-506; Memory; Nicotine; SL-327; VGCC blockers