Protective effects of chronic lithium treatment against spatial memory retention deficits induced by the protein kinase AII inhibitor H-89 in rats.
We have previously shown that infusion of the PKAII inhibitor H-89 in the CA1 area of the hippocampus impaired spatial memory retention. There is some evidence suggesting the neuroprotective effects of chronic lithium administration including its ability to attenuate a deleterious effect of chronic stress on spatial memory in rats. In the present study, we investigated whether chronic administration of lithium can improve memory as well as influence the inhibitory effect of H-89 on spatial memory retention. Male albino rats were treated systemically with lithium (600 mg/l) for 4 weeks and then trained for 4 days in the Morris water maze. Testing the animals 48 h later showed a significant reduction in escape latency (p < 0.05) and travel distance (p < 0.05) compared to the controls. In separate experiments, the rats were similarly treated with lithium for 4 weeks, followed by similar training for 4 days and then immediately infused bilaterally with vehicle or 5 micromol/l H-89 into the CA1 region of the hippocampus. Animals were then tested 48 h after H-89 infusion in order to assess their spatial memory retention. The lithium treatment caused a significant reduction in escape latency (p < 0.001) and travel distance (p < 0.001) compared to H-89-treated animals. The data suggest that lithium treatment for 4 weeks improved spatial memory retention and that lithium pretreatment prevented or reversed the H-89-induced spatial memory deficits.
Sharifzadeh
Mohammad
M
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. msharifzadeh@sina.tums.ac.ir
Aghsami
Mehdi
M
Gholizadeh
Shervin
S
Tabrizian
Kaveh
K
Soodi
Maliheh
M
Khalaj
Siavash
S
Ranjbar
Akram
A
Hosseini-Sharifabad
Ali
A
Roghani
Ali
A
Karimfar
Mohammad H
MH
D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000097:blood; D001522:Behavior, Animal / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007546:Isoquinolines / Q000494:pharmacology*; D018021:Lithium Chloride / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*
D018692:Antimanic Agents; D007546:Isoquinolines; D013449:Sulfonamides; D017868:Cyclic AMP-Dependent Protein Kinases; D018021:Lithium Chloride; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide