Marinobufagenin (MBG) suppression of ethanol-seeking behavior is associated with inhibition of brain cortex Na/K-ATPase in mice.
In the present study the hypothesis was tested that sodium pump ligands (SPL) can modulate alcohol-seeking behavior and that this effect is related to changes in Na/K-ATPase activity in the central nervous system. Mice were tested for initiation of ethanol intravenous self-administration (IVSA) following i.p. pretreatment with vehicle or the endogenous SPL, marinobufagenin (MBG). Drug- and experimentally-naive mice acquired IVSA of 2% ethanol during a single 30-min session. MBG was found to dose-dependently attenuate (1.25-2.5 microg/kg) initiation of ethanol IVSA producing a decrease in the ratio and in the difference between operant responses of response-dependent and yoked animals as well as a decrease in percentage of mice demonstrating ethanol-seeking behavior. Attenuation of the reinforcing effect of ethanol resulting from MBG was associated with brain levels of this steroid capable of concurrently inhibiting Na/K-ATPase in the brain cortex. We hypothesize that endogenous digitalis-like factors could modulate the reinforcing effect of ethanol.
Kashkin
Vladimir A
VA
Department of Psychopharmacology, Valdman Institute of Pharmacology, Pavlov Medical University, 6/8 Lev Tolstoy Street, St. Petersburg 197089, Russia.
Bagrov
Alexei Y
AY
Fedorova
Olga V
OV
Bagrov
Yakov Y
YY
Agalakova
Natalia I
NI
Patkina
Nadezhda A
NA
Zvartau
Edwin E
EE
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000201:enzymology; D002018:Bufanolides / Q000494:pharmacology / Q000627:therapeutic use*; D002298:Cardenolides; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004077:Digoxin; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012503:Saponins / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D002018:Bufanolides; D002298:Cardenolides; D004791:Enzyme Inhibitors; D012503:Saponins; C034504:digoxin-like factors; C093896:marinobufagenin; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase