Role of CA2+/calmodulin on ethanol neurobehavioral effects.
BACKGROUND
The cAMP-dependent protein kinase A (PKA) signaling transduction pathway has been shown to play an important role in the modulation of several ethanol-induced behaviors. Different studies have demonstrated intracellular calcium (Ca(2+))-dependent activation of the PKA cascade after ethanol administration. Thus, the cAMP cascade mediator Ca(2+)-dependent calmodulin (CaM) has been strongly implicated in the central effects of ethanol.


OBJECTIVE
In this study, we assessed the role of the CaM inhibitor W7 on ethanol-induced stimulation, ethanol intake, and ethanol-induced activation of PKA.


METHODS
Swiss mice were pretreated with W7 (0-10 mg/kg) 30 min before ethanol (0-3.75 g/kg) administration. Immediately, animals were placed during 20 min in an open-field chamber. Ethanol (10 %, v/v) intake in 2 h was assessed using a limited access paradigm. Experiments with caffeine (0-15 mg/kg), cocaine (0-4 mg/kg), and saccharine (0.1 %, w/v) were designed to compare their results to those obtained with ethanol. Western blot was assayed 45 min after ethanol administration.


RESULTS
Results showed that pretreatment with W7, reduced selectively in a dose-dependent fashion ethanol-induced locomotor stimulation and ethanol intake. The ethanol-induced activation of PKA was also prevented by W7 administration.


CONCLUSIONS
These results demonstrate that CaM inhibition resulted in a selective reduction of ethanol-stimulating effects and ethanol intake. The PKA activation induced by ethanol was blocked after the CaM blockade with W7. These results provide further evidence of the key role of cellular Ca(2+)-dependent pathways on the central effects of ethanol.
Área de Psicobiología, Universtitat Jaume I, Avda. Sos Baynat s/n, 12071, Castellón, Spain, balino@uji.es.
Pablo
P
Baliño
Juan Carlos
JC
Ledesma
Carlos M G
CM
Aragon
D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000494:pharmacology
D004791:Enzyme Inhibitors; D013449:Sulfonamides; D000431:Ethanol; C017967:W 7; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium