{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T09:43:56Z","timestamp":1762249436957,"version":"3.40.4"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T00:00:00Z","timestamp":1381449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2014,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\u2010dependent protein kinase (<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>) signaling transduction pathway has been shown to play an important role in the modulation of several ethanol (EtOH)\u2010induced behavioral actions. In vivo, short\u2010term exposure to EtOH up\u2010regulates the<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\u2010signaling cascade. Interestingly, different<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010dependent<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content>\u2013<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>cascade mediators play a critical role in the neurobehavioral response to EtOH, being of special relevance to the<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010dependent adenylyl cyclases 1 and 8. We hypothesize an intracellular<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>activation elicited by EtOH administration, which may be regulated by a<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>\u2010dependent mechanism as an early cellular response. Thus, the present work aims to explore the role of<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>(internal and external) on the EtOH\u2010activated<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>cascade.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Swiss male mice received an intraperitoneal injection of EtOH (0 or 4\u00a0g\/kg), and brains were dissected following a temporal pattern (7, 15, 30, 45, 90, or 120\u00a0minutes). Either the enzymatic<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>activity or its fingerprint was analyzed on different brain areas (cortex, hypothalamus, hippocampus, and striatum). To explore the role of<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>on the EtOH\u2010activated<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>cascade, mice were pretreated with diltiazem (0 or 20\u00a0mg\/kg), dantrolene (0 or 5\u00a0mg\/kg), or 3,7\u2010<jats:styled-content style=\"fixed-case\">D<\/jats:styled-content>imethyl\u20101\u2010(2\u2010propynyl)xanthine (0 or 1\u00a0mg\/kg) 30\u00a0minutes before EtOH (4\u00a0g\/kg) administration. After 45\u00a0minutes of EtOH administration, brains were removed and dissected to measure the<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>activity or its fingerprint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Results from these experiments showed an EtOH\u2010dependent activation of<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>in different brain areas. Manipulations involving a disruption of intracellular<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>release from the endoplasmic reticulum resulted in a decreased EtOH\u2010induced activation of<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>. On the contrary, extracellular\u2010to\u2010cytoplasm<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>manipulations did not prevent the<jats:styled-content style=\"fixed-case\">PKA<\/jats:styled-content>activation by EtOH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Altogether, these results show the critical role of stored<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>a<jats:sup>2+<\/jats:sup>as an intracellular mediator of different neurobiological actions of EtOH and provide further evidence of a possible new target for EtOH within the central nervous system.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.12289","type":"journal-article","created":{"date-parts":[[2013,10,14]],"date-time":"2013-10-14T11:53:56Z","timestamp":1381751636000},"page":"629-640","source":"Crossref","is-referenced-by-count":12,"title":["In Vivo Study of Ethanol\u2010Activated Brain Protein Kinase A: Manipulations of Ca<sup>2+<\/sup>Distribution and Flux"],"prefix":"10.1111","volume":"38","author":[{"given":"Pablo","family":"Bali\u00f1o","sequence":"first","affiliation":[{"name":"Area de Psicobiologia Universitat Jaume I Castell\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Carlos","family":"Ledesma","sequence":"additional","affiliation":[{"name":"Area de Psicobiologia Universitat Jaume I Castell\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos M. G.","family":"Aragon","sequence":"additional","affiliation":[{"name":"Area de Psicobiologia Universitat Jaume I Castell\u00f3n Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,10,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.301.1.66"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.05.107"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.01.016"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.01.036"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0898-6568(94)00092-P"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80510-3"},{"key":"e_1_2_6_8_1","first-page":"391","article-title":"Calcium channel antagonists attenuate cross\u2010 sensitization to the locomotor effects of nicotine and ethanol in mice","volume":"56","author":"Biala G","year":"2004","journal-title":"Pol J Pharmacol"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1054\/ceca.1999.0071"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.2741\/blacksto"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32700-X"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91639-I"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/35.2.134"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005697"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/S0022-3565(25)22827-0","article-title":"Ethanol and inositol 1,4,5\u2010trisphosphate release calcium from separate stores of brain microsomes","volume":"250","author":"Daniell LC","year":"1989","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(88)90375-8"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(95)02054-3"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.1.1"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10217"},{"key":"e_1_2_6_20_1","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/S0022-3565(24)36530-9","article-title":"Beta adrenergic sensitization of gamma\u2010aminobutyric acid receptors to ethanol involves a cyclic AMP\/protein kinase A second\u2010messenger mechanism","volume":"280","author":"Freund RK","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.08.040"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1369-1600.2011.00336.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.126144"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1441.022"},{"key":"e_1_2_6_25_1","first-page":"930","article-title":"Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal","volume":"24","author":"Li J","year":"2003","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4273-04.2005"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2003.10.002"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01456-X"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1016\/S0021-9258(19)39923-5","article-title":"Ethanol increases extracellular adenosine by inhibiting adenosine uptake via the nucleoside transporter","volume":"265","author":"Nagy LE","year":"1990","journal-title":"J Biol Chem"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80983-6"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2005.07.004"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.01.117"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24381"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(01)00707-9"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2007.11.001"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-13-04809.2000"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.94.240"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)93016-4"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.05.046"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-10-j0003.2000"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2007.00425.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S0022-3565(24)38104-2","article-title":"Necessary role for ventral tegmental area adenylate cyclase and protein kinase A in induction of behavioral sensitization to intraventral tegmental area amphetamine","volume":"289","author":"Tolliver BK","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_43_1","doi-asserted-by":"crossref","first-page":"5297","DOI":"10.1523\/JNEUROSCI.21-14-05297.2001","article-title":"The cAMP\u2010Protein kinaseA signal transduction pathway modulates EtOH consumption and sedative effects of EtOH","volume":"21","author":"Wand G","year":"2001","journal-title":"J Neurosci"},{"key":"e_1_2_6_44_1","doi-asserted-by":"crossref","first-page":"9710","DOI":"10.1523\/JNEUROSCI.23-30-09710.2003","article-title":"Type 8 adenylyl cyclase is targeted to excitatory synapses and required for mossy fiber long\u2010term potentiation","volume":"23","author":"Wang H","year":"2003","journal-title":"J Neurosci"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1997.tb04502.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01088-3"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67062390.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)80036-2"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.1.220"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.08.004"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1998.tb08262.x"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0159"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/20200"}],"container-title":["Alcoholism: Clinical and Experimental Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Facer.12289","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acer.12289","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T17:00:49Z","timestamp":1746032449000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acer.12289"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10,11]]},"references-count":52,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3]]}},"alternative-id":["10.1111\/acer.12289"],"URL":"https:\/\/doi.org\/10.1111\/acer.12289","archive":["Portico"],"relation":{},"ISSN":["0145-6008","1530-0277"],"issn-type":[{"type":"print","value":"0145-6008"},{"type":"electronic","value":"1530-0277"}],"subject":[],"published":{"date-parts":[[2013,10,11]]}}}