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Role of CA2+/calmodulin on ethanol neurobehavioral effects

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Abstract

Rationale

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 (Ca2+)-dependent activation of the PKA cascade after ethanol administration. Thus, the cAMP cascade mediator Ca2+-dependent calmodulin (CaM) has been strongly implicated in the central effects of ethanol.

Objectives

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 Ca2+-dependent pathways on the central effects of ethanol.

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Acknowledgments

This research was supported by a grant from Ministerio de Ciéncia e Innovación (PSI2011-28934/PSIC). Baliño P was supported by a fellowship from the CICYT (BES-2009-024438). Ledesma JC was supported by a fellowship from Universitat Jaume I (PREDOC/2007/07), Spain.

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  1. Área de Psicobiología, Universtitat Jaume I, Avda. Sos Baynat s/n, 12071, Castellón, Spain

    Pablo Baliño, Juan Carlos Ledesma & Carlos M. G. Aragon

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  1. Pablo Baliño
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  2. Juan Carlos Ledesma
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  3. Carlos M. G. Aragon
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Correspondence to Carlos M. G. Aragon.

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Baliño, P., Ledesma, J.C. & Aragon, C.M.G. Role of CA2+/calmodulin on ethanol neurobehavioral effects. Psychopharmacology 231, 4611–4621 (2014). https://doi.org/10.1007/s00213-014-3610-6

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