Post-training intrahippocampal infusion of nicotine-bucladesine combination causes a synergistic enhancement effect on spatial memory retention in rats.
We previously had shown that bilateral intrahippocampal infusion of 1 microg nicotine (but not 0.5 microg dose) led to an improvement in spatial memory retention in the Morris water maze task in male rats. We also reported that a similar type of bilateral infusion of H89, a protein kinase AII (PKA II) inhibitor, caused a deficit in spatial memory retention. In the present study, we wished to test the hypothesis that intrahippocampal infusion of dibutyryl cyclic AMP (DB-cAMP also called bucladesine), a membrane permeable selective activator of PKA, into the CA1 region can cause an improvement in spatial memory in this maze task. Indeed, bilateral infusion of 10 and 100 microM bucladesine (but not 1 and 5 microM doses) led to a significant reduction in escape latency and travel distance (showing an improvement in spatial memory) compared to the control. Also, bilateral infusion of 0.5 microg nicotine or 1 microM bucladesine alone did not lead to an improvement in spatial memory. However, such bilateral infusion of bucladesine at 1 and 5 microM concentrations infused within minutes after 0.5 microg nicotine infusion improved spatial memory retention. Taken together, our data suggest that intrahippocampal bucladesine infusions improve spatial memory retention in male rats and that bucladesine can interact synergistically with nicotine to improve spatial memory.
Sharifzadeh
Mohammad
M
Department of Pharmacology and Toxicology, Pharmaceutical Sciences and Medicinal Plants Research Centers, Tehran University of Medical Sciences, Tehran, Iran. msharifzadeh@tums.ac.ir
Zamanian
Ali-Reza
AR
Gholizadeh
Shervin
S
Tabrizian
Kaveh
K
Etminani
Maryam
M
Khalaj
Siavash
S
Zarrindast
Mohammad-Reza
MR
Roghani
Ali
A
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006624:Hippocampus; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012153:Retention, Psychology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013028:Space Perception / Q000187:drug effects
D018722:Nicotinic Agonists; D003994:Bucladesine; D009538:Nicotine; D017868:Cyclic AMP-Dependent Protein Kinases