Skip to main content

Advertisement

SpringerLink
Log in

Increased operant responding for ethanol in male C57BL/6J mice: specific regulation by the ERK1/2, but not JNK, MAP kinase pathway

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Extracellular signal-regulated protein kinase (ERK1/2) is a member of the mitogen-activated protein kinase (MAPK) signaling pathway and a key molecular target for ethanol (EtOH) and other drugs of abuse.

Objective

The aim of the study was to assess the role of two MAPK pathways, ERK1/2 and c-Jun N-terminal kinase (JNK), on the modulation of EtOH and sucrose self-administration.

Materials and methods

C57BL/6J mice were trained to lever press on a fixed-ratio 4 schedule with 9% EtOH/2% sucrose, or 2% sucrose, as the reinforcer. In experiments 1 and 2, mice were injected with the MEK1/2 inhibitor SL 327 (0–100 mg/kg) and the JNK inhibitor AS 6012452 (0–56 mg/kg) prior to self-administration. In experiment 3, SL 327 (0–100 mg/kg) was administered prior to performance on a progressive ratio (PR) schedule of EtOH reinforcement. In experiment 4, SL 327 and AS 601245 were injected 2 h before a locomotor test.

Results

SL 327 (30 mg/kg) significantly increased EtOH self-administration without affecting locomotion. Higher doses of SL 327 and AS 601245 reduced EtOH-reinforced responding and locomotor activity. Reductions of both ligands on sucrose self-administration were due to decreases in motor activity. SL 327 pretreatment had no effect on PR responding.

Conclusions

ERK1/2 activity is more directly involved in modulating the reinforcing properties of EtOH than JNK activity due to its selective potentiation of EtOH-reinforced responding. The specificity of this effect to EtOH self-administration, rather than sucrose self-administration, suggests that the mechanism by which ERK1/2 increases EtOH-reinforced responding does not generalize to all reinforcing solutions and is not due to increased motivation to consume EtOH.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adams JP, Sweatt JD (2002) Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu Rev Pharmacol Toxicol 42:135–163

    PubMed  CAS  Google Scholar 

  • Adams JP, Roberson ED, English JD, Selcher JC, Sweatt JD (2000) MAPK regulation of gene expression in the central nervous system. Acta Neurobiol Exp (Wars) 60:377–394

    CAS  Google Scholar 

  • Arolfo MP, Yao L, Gordon AS, Diamond I, Janak PH (2004) Ethanol operant self-administration in rats is regulated by adenosine A2 receptors. Alcohol Clin Exp Res 28:1308–1316

    PubMed  CAS  Google Scholar 

  • Atkins CM, Selcher JC, Petraitis JJ, Trzaskos JM, Sweatt JD (1998) The MAPK cascade is required for mammalian associative learning. Nat Neurosci 1:602–609

    PubMed  CAS  Google Scholar 

  • Bachtell RK, Tsivkovskaia NO, Ryabinin AE (2002) Alcohol-induced c-Fos expression in the Edinger-Westphal nucleus: pharmacological and signal transduction mechanisms. J Pharmacol Exp Ther 302:516–524

    PubMed  CAS  Google Scholar 

  • Backstrom P, Bachteler D, Koch S, Hyytia P, Spanagel R (2004) mGluR5 antagonist MPEP reduces ethanol-seeking and relapse behavior. Neuropsychopharmacology 29:921–928

    PubMed  Google Scholar 

  • Besheer J, Stevenson RA, Hodge CW (2006) mGlu5 receptors are involved in the discriminative stimulus effects of self-administered ethanol in rats. Eur J Pharmacol 551:71–75

    PubMed  CAS  Google Scholar 

  • Besheer J, Faccidomo S, Grondin JJ, Hodge CW (2008) Regulation of motivation to self-administer ethanol by mGluR5 in alcohol-preferring (P) rats. Alcohol Clin Exp Res 32:209–221

    PubMed  CAS  Google Scholar 

  • Bevilaqua LR, Kerr DS, Medina JH, Izquierdo I, Cammarota M (2003) Inhibition of hippocampal Jun N-terminal kinase enhances short-term memory but blocks long-term memory formation and retrieval of an inhibitory avoidance task. Eur J Neurosci 17:897–902

    PubMed  Google Scholar 

  • Borsello T, Croquelois K, Hornung JP, Clarke PG (2003) N-methyl-d-aspartate-triggered neuronal death in organotypic hippocampal cultures is endocytic, autophagic and mediated by the c-Jun N-terminal kinase pathway. Eur J Neurosci 18:473–485

    PubMed  Google Scholar 

  • Boulton TG, Cobb MH (1991) Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies. Cell Regul 2:357–371

    PubMed  CAS  Google Scholar 

  • Brown G, Stephens DN (2002) Effects of cocaine on responding for ethanol or sucrose under a progressive ratio schedule. Behav Pharmacol 13:157–162

    PubMed  CAS  Google Scholar 

  • Carboni S, Hiver A, Szyndralewiez C, Gaillard P, Gotteland JP, Vitte PA (2004) AS601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties. J Pharmacol Exp Ther 310:25–32

    PubMed  CAS  Google Scholar 

  • Carboni S, Boschert U, Gaillard P, Gotteland JP, Gillon JY, Vitte PA (2008) AS601245, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduces axon/dendrite damage and cognitive deficits after global cerebral ischaemia in gerbils. Br J Pharmacol 153:157–163

    PubMed  CAS  Google Scholar 

  • Carnicella S, Kharazia V, Jeanblanc J, Janak PH, Ron D (2008) GDNF is a fast-acting potent inhibitor of alcohol consumption and relapse. Proc Natl Acad Sci U S A 105:8114–8119

    PubMed  CAS  Google Scholar 

  • Cestari V, Costanzi M, Castellano C, Rossi-Arnaud C (2006) A role for ERK2 in reconsolidation of fear memories in mice. Neurobiol Learn Mem 86:133–143

    PubMed  CAS  Google Scholar 

  • Chandler LJ (2003) Ethanol and brain plasticity: receptors and molecular networks of the postsynaptic density as targets of ethanol. Pharmacol Ther 99:311–326

    PubMed  CAS  Google Scholar 

  • Chandler LJ, Sutton G (2005) Acute ethanol inhibits extracellular signal-regulated kinase, protein kinase B, and adenosine 3′:5′-cyclic monophosphate response element binding protein activity in an age- and brain region-specific manner. Alcohol Clin Exp Res 29:672–682

    PubMed  CAS  Google Scholar 

  • Chen RH, Sarnecki C, Blenis J (1992) Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol Cell Biol 12:915–927

    PubMed  CAS  Google Scholar 

  • Choe ES, Wang JQ (2001) Group I metabotropic glutamate receptors control phosphorylation of CREB, Elk-1 and ERK via a CaMKII-dependent pathway in rat striatum. Neurosci Lett 313:129–132

    PubMed  CAS  Google Scholar 

  • Choe ES, Chung KT, Mao L, Wang JQ (2002) Amphetamine increases phosphorylation of extracellular signal-regulated kinase and transcription factors in the rat striatum via group I metabotropic glutamate receptors. Neuropsychopharmacology 27:565–575

    PubMed  CAS  Google Scholar 

  • Crews CM, Erikson RL (1992) Purification of a murine protein-tyrosine/threonine kinase that phosphorylates and activates the Erk-1 gene product: relationship to the fission yeast byr1 gene product. Proc Natl Acad Sci U S A 89:8205–8209

    PubMed  CAS  Google Scholar 

  • Czachowski CL, Legg BH, Samson HH (2003) Assessment of sucrose and ethanol reinforcement: the across-session breakpoint procedure. Physiol Behav 78:51–59

    PubMed  CAS  Google Scholar 

  • Davis S, Vanhoutte P, Pages C, Caboche J, Laroche S (2000) The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci 20:4563–4572

    PubMed  CAS  Google Scholar 

  • Duvarci S, Nader K, LeDoux JE (2005) Activation of extracellular signal-regulated kinase-mitogen-activated protein kinase cascade in the amygdala is required for memory reconsolidation of auditory fear conditioning. Eur J Neurosci 21:283–289

    PubMed  Google Scholar 

  • Economidou D, Mattioli L, Cifani C, Perfumi M, Massi M, Cuomo V, Trabace L, Ciccocioppo R (2006) Effect of the cannabinoid CB1 receptor antagonist SR-141716A on ethanol self-administration and ethanol-seeking behaviour in rats. Psychopharmacology (Berl) 183:394–403

    CAS  Google Scholar 

  • Ettenberg A, Pettit HO, Bloom FE, Koob GF (1982) Heroin and cocaine intravenous self-administration in rats: mediation by separate neural systems. Psychopharmacology (Berl) 78:204–209

    CAS  Google Scholar 

  • Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, Feeser WS, Van Dyk DE, Pitts WJ, Earl RA, Hobbs F, Copeland RA, Magolda RL, Scherle PA, Trzaskos JM (1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J Biol Chem 273:18623–18632

    PubMed  CAS  Google Scholar 

  • Ferguson SM, Fasano S, Yang P, Brambilla R, Robinson TE (2006) Knockout of ERK1 enhances cocaine-evoked immediate early gene expression and behavioral plasticity. Neuropsychopharmacology 31:2660–2668

    PubMed  CAS  Google Scholar 

  • Ford MM, Eldridge JC, Samson HH (2004) Determination of an estradiol dose–response relationship in the modulation of ethanol intake. Alcohol Clin Exp Res 28:20–28

    PubMed  CAS  Google Scholar 

  • Ford MM, Nickel JD, Phillips TJ, Finn DA (2005) Neurosteroid modulators of GABA(A) receptors differentially modulate ethanol intake patterns in male C57BL/6J mice. Alcohol Clin Exp Res 29:1630–1640

    PubMed  CAS  Google Scholar 

  • Gaillard P, Jeanclaude-Etter I, Ardissone V, Arkinstall S, Cambet Y, Camps M, Chabert C, Church D, Cirillo R, Gretener D, Halazy S, Nichols A, Szyndralewiez C, Vitte PA, Gotteland JP (2005) Design and synthesis of the first generation of novel potent, selective, and in vivo active (benzothiazol-2-yl)acetonitrile inhibitors of the c-Jun N-terminal kinase. J Med Chem 48:4596–4607

    PubMed  CAS  Google Scholar 

  • Gerdjikov TV, Ross GM, Beninger RJ (2004) Place preference induced by nucleus accumbens amphetamine is impaired by antagonists of ERK or p38 MAP kinases in rats. Behav Neurosci 118:740–750

    PubMed  CAS  Google Scholar 

  • Grant BF, Dawson DA, Stinson FS, Chou SP, Dufour MC, Pickering RP (2004) The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991–1992 and 2001–2002. Drug Alcohol Depend 74:223–234

    PubMed  Google Scholar 

  • Grewal SS, York RD, Stork PJ (1999) Extracellular-signal-regulated kinase signalling in neurons. Curr Opin Neurobiol 9:544–553

    PubMed  CAS  Google Scholar 

  • Hendrickson RJ, Cahill PA, McKillop IH, Sitzmann JV, Redmond EM (1998) Ethanol inhibits mitogen activated protein kinase activity and growth of vascular smooth muscle cells in vitro. Eur J Pharmacol 362:251–259

    PubMed  CAS  Google Scholar 

  • Herdegen T, Claret FX, Kallunki T, Martin-Villalba A, Winter C, Hunter T, Karin M (1998) Lasting N-terminal phosphorylation of c-Jun and activation of c-Jun N-terminal kinases after neuronal injury. J Neurosci 18:5124–5135

    PubMed  CAS  Google Scholar 

  • Hodge CW, Samson HH, Haraguchi M (1992) Microinjections of dopamine agonists in the nucleus accumbens increase ethanol-reinforced responding. Pharmacol Biochem Behav 43:249–254

    PubMed  CAS  Google Scholar 

  • Hodge CW, Chappelle AM, Samson HH (1995) GABAergic transmission in the nucleus accumbens is involved in the termination of ethanol self-administration in rats. Alcohol Clin Exp Res 19:1486–1493

    PubMed  CAS  Google Scholar 

  • Hodge CW, Miles MF, Sharko AC, Stevenson RA, Hillmann JR, Lepoutre V, Besheer J, Schroeder JP (2006) The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology (Berl) 183:429–438

    CAS  Google Scholar 

  • Huang TY, Lin CH (2006) Role of amygdala MAPK activation on immobility behavior of forced swim rats. Behav Brain Res 173:104–111

    PubMed  CAS  Google Scholar 

  • Impey S, Obrietan K, Storm DR (1999) Making new connections: role of ERK/MAP kinase signaling in neuronal plasticity. Neuron 23:11–14

    PubMed  CAS  Google Scholar 

  • Janak PH, Redfern JE, Samson HH (1998) The reinforcing effects of ethanol are altered by the endogenous neurosteroid, allopregnanolone. Alcohol Clin Exp Res 22:1106–1112

    PubMed  CAS  Google Scholar 

  • Kalluri HS, Ticku MK (2002) Ethanol-mediated inhibition of mitogen-activated protein kinase phosphorylation in mouse brain. Eur J Pharmacol 439:53–58

    PubMed  CAS  Google Scholar 

  • Kelley SP, Nannini MA, Bratt AM, Hodge CW (2001) Neuropeptide-Y in the paraventricular nucleus increases ethanol self-administration. Peptides 22:515–522

    PubMed  CAS  Google Scholar 

  • Koob GF, Pettit HO, Ettenberg A, Bloom FE (1984) Effects of opiate antagonists and their quaternary derivatives on heroin self-administration in the rat. J Pharmacol Exp Ther 229:481–486

    PubMed  CAS  Google Scholar 

  • Koob GF, Le HT, Creese I (1987) The D1 dopamine receptor antagonist SCH 23390 increases cocaine self-administration in the rat. Neurosci Lett 79:315–320

    PubMed  CAS  Google Scholar 

  • Krishna M, Narang H (2008) The complexity of mitogen-activated protein kinases (MAPKs) made simple. Cell Mol Life Sci 65(22):3525–3544

    PubMed  CAS  Google Scholar 

  • Kuroda KO, Meaney MJ, Uetani N, Fortin Y, Ponton A, Kato T (2007) ERK-FosB signaling in dorsal MPOA neurons plays a major role in the initiation of parental behavior in mice. Mol Cell Neurosci 36:121–131

    PubMed  CAS  Google Scholar 

  • Lominac KD, Kapasova Z, Hannun RA, Patterson C, Middaugh LD, Szumlinski KK (2006) Behavioral and neurochemical interactions between Group 1 mGluR antagonists and ethanol: potential insight into their anti-addictive properties. Drug Alcohol Depend 85:142–156

    PubMed  CAS  Google Scholar 

  • Lu L, Hope BT, Dempsey J, Liu SY, Bossert JM, Shaham Y (2005) Central amygdala ERK signaling pathway is critical to incubation of cocaine craving. Nat Neurosci 8:212–219

    PubMed  CAS  Google Scholar 

  • Lu L, Koya E, Zhai H, Hope BT, Shaham Y (2006) Role of ERK in cocaine addiction. Trends Neurosci 29:695–703

    PubMed  CAS  Google Scholar 

  • Markou A, Weiss F, Gold LH, Caine SB, Schulteis G, Koob GF (1993) Animal models of drug craving. Psychopharmacology (Berl) 112:163–182

    CAS  Google Scholar 

  • Mazzucchelli C, Brambilla R (2000) Ras-related and MAPK signalling in neuronal plasticity and memory formation. Cell Mol Life Sci 57:604–611

    PubMed  CAS  Google Scholar 

  • Mazzucchelli C, Vantaggiato C, Ciamei A, Fasano S, Pakhotin P, Krezel W, Welzl H, Wolfer DP, Pages G, Valverde O, Marowsky A, Porrazzo A, Orban PC, Maldonado R, Ehrengruber MU, Cestari V, Lipp HP, Chapman PF, Pouyssegur J, Brambilla R (2002) Knockout of ERK1 MAP kinase enhances synaptic plasticity in the striatum and facilitates striatal-mediated learning and memory. Neuron 34:807–820

    PubMed  CAS  Google Scholar 

  • McMillen BA, Crawford MS, Kulers CM, Williams HL (2005) Effects of a metabotropic, mglu5, glutamate receptor antagonist on ethanol consumption by genetic drinking rats. Alcohol 40:494–497

    CAS  Google Scholar 

  • Mitchell JM, Liang MT, Fields HL (2005) A single injection of the kappa opioid antagonist norbinaltorphimine increases ethanol consumption in rats. Psychopharmacology (Berl) 182:384–392

    CAS  Google Scholar 

  • Mukherjee PK, DeCoster MA, Campbell FZ, Davis RJ, Bazan NG (1999) Glutamate receptor signaling interplay modulates stress-sensitive mitogen-activated protein kinases and neuronal cell death. J Biol Chem 274:6493–6498

    PubMed  CAS  Google Scholar 

  • National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington

    Google Scholar 

  • Ortiz J, Harris HW, Guitart X, Terwilliger RZ, Haycock JW, Nestler EJ (1995) Extracellular signal-regulated protein kinases (ERKs) and ERK kinase (MEK) in brain: regional distribution and regulation by chronic morphine. J Neurosci 15:1285–1297

    PubMed  CAS  Google Scholar 

  • Oster SM, Toalston JE, Kuc KA, Pommer TJ, Murphy JM, Lumeng L, Bell RL, McBride WJ, Rodd ZA (2006) Effects of multiple alcohol deprivations on operant ethanol self-administration by high-alcohol-drinking replicate rat lines. Alcohol 38:155–164

    PubMed  CAS  Google Scholar 

  • Quirarte GL, Reid LD, de la Teja IS, Reid ML, Sanchez MA, Diaz-Trujillo A, Aguilar-Vazquez A, Prado-Alcala RA (2007) Estradiol valerate and alcohol intake: dose–response assessments. BMC Pharmacol 7:3

    PubMed  Google Scholar 

  • Reid LD, Marinelli PW, Bennett SM, Fiscale LT, Narciso SP, Oparowski CJ, Reid ML, Merrigan BA, Moricone J, Hubbell CL, Gianoulakis C (2002) One injection of estradiol valerate induces dramatic changes in rats’ intake of alcoholic beverages. Pharmacol Biochem Behav 72:601–616

    PubMed  CAS  Google Scholar 

  • Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11

    PubMed  CAS  Google Scholar 

  • Robinson MJ, Cobb MH (1997) Mitogen-activated protein kinase pathways. Curr Opin Cell Biol 9:180–186

    PubMed  CAS  Google Scholar 

  • Rodd ZA, Bell RL, Kuc KA, Murphy JM, Lumeng L, Li TK, McBride WJ (2003) Effects of repeated alcohol deprivations on operant ethanol self-administration by alcohol-preferring (P) rats. Neuropsychopharmacology 28:1614–1621

    PubMed  CAS  Google Scholar 

  • Russo SJ, Mazei-Robison MS, Ables JL, Nestler EJ (2008) Neurotrophic factors and structural plasticity in addiction. Neuropharmacology (in press)

  • Sabino V, Cottone P, Steardo L, Schmidhammer H, Zorrilla EP (2007) 14-Methoxymetopon, a highly potent mu opioid agonist, biphasically affects ethanol intake in Sardinian alcohol-preferring rats. Psychopharmacology (Berl) 192:537–546

    CAS  Google Scholar 

  • Salzmann J, Marie-Claire C, Le Guen S, Roques BP, Noble F (2003) Importance of ERK activation in behavioral and biochemical effects induced by MDMA in mice. Br J Pharmacol 140:831–838

    PubMed  CAS  Google Scholar 

  • Samson HH (1986) Initiation of ethanol reinforcement using a sucrose-substitution procedure in food- and water-sated rats. Alcohol Clin Exp Res 10:436–442

    PubMed  CAS  Google Scholar 

  • Sanna PP, Simpson C, Lutjens R, Koob G (2002) ERK regulation in chronic ethanol exposure and withdrawal. Brain Res 948:186–191

    PubMed  CAS  Google Scholar 

  • Schafe GE, Atkins CM, Swank MW, Bauer EP, Sweatt JD, LeDoux JE (2000) Activation of ERK/MAP kinase in the amygdala is required for memory consolidation of pavlovian fear conditioning. J Neurosci 20:8177–787

    PubMed  CAS  Google Scholar 

  • Schroeder JP, Overstreet DH, Hodge CW (2005) The mGluR5 antagonist MPEP decreases operant ethanol self-administration during maintenance and after repeated alcohol deprivations in alcohol-preferring (P) rats. Psychopharmacology (Berl) 179:262–270

    CAS  Google Scholar 

  • Schroeder JP, Spanos M, Stevenson JR, Besheer J, Salling M, Hodge CW (2008) Cue-induced reinstatement of alcohol-seeking behavior is associated with increased ERK1/2 phosphorylation in specific limbic brain regions: blockade by the mGluR5 antagonist MPEP. Neuropharmacology 55:546–554

    PubMed  CAS  Google Scholar 

  • Schwarzschild MA, Cole RL, Hyman SE (1997) Glutamate, but not dopamine, stimulates stress-activated protein kinase and AP-1-mediated transcription in striatal neurons. J Neurosci 17:3455–3466

    PubMed  CAS  Google Scholar 

  • Seger R, Krebs EG (1995) The MAPK signaling cascade. FASEB J 9:726–735

    PubMed  CAS  Google Scholar 

  • Selcher JC, Atkins CM, Trzaskos JM, Paylor R, Sweatt JD (1999) A necessity for MAP kinase activation in mammalian spatial learning. Learn Mem 6:478–490

    PubMed  CAS  Google Scholar 

  • Sgambato V, Vanhoutte P, Pages C, Rogard M, Hipskind R, Besson MJ, Caboche J (1998) In vivo expression and regulation of Elk-1, a target of the extracellular-regulated kinase signaling pathway, in the adult rat brain. J Neurosci 18:214–226

    PubMed  CAS  Google Scholar 

  • Sharko AC, Hodge CW (2007) Acute ethanol challenge modulates extracellular-signal regulated kinase phosphorylation in vivo. Alcohol Clin Exp Res 31:193A

    Google Scholar 

  • Shi X, McGinty JF (2006) Extracellular signal-regulated mitogen-activated protein kinase inhibitors decrease amphetamine-induced behavior and neuropeptide gene expression in the striatum. Neuroscience 138:1289–1298

    PubMed  CAS  Google Scholar 

  • Sinnott RS, Phillips TJ, Finn DA (2002) Alteration of voluntary ethanol and saccharin consumption by the neurosteroid allopregnanolone in mice. Psychopharmacology (Berl) 162:438–447

    CAS  Google Scholar 

  • Spanos M, Hodge CW (2008) Neuroadaptive changes in ERK1/2 activity associated with alcohol self-administration in mice. Alcohol Clin Exp Res 32:162A–162A

    Google Scholar 

  • Stafford D, LeSage MG, Glowa JR (1998) Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review. Psychopharmacology (Berl) 139:169–184

    CAS  Google Scholar 

  • Sweatt JD (2004) Mitogen-activated protein kinases in synaptic plasticity and memory. Curr Opin Neurobiol 14:311–317

    PubMed  CAS  Google Scholar 

  • Thomas GM, Huganir RL (2004) MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5:173–183

    PubMed  CAS  Google Scholar 

  • Tomkins DM, Higgins GA, Sellers EM (1994) Low doses of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH DPAT) increase ethanol intake. Psychopharmacology (Berl) 115:173–179

    CAS  Google Scholar 

  • Treisman R (1996) Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 8:205–215

    PubMed  CAS  Google Scholar 

  • Tsuji R, Guizzetti M, Costa LG (2003) In vivo ethanol decreases phosphorylated MAPK and p70S6 kinase in the developing rat brain. Neuroreport 14:1395–1399

    PubMed  CAS  Google Scholar 

  • Ulm RR, Volpicelli JR, Volpicelli LA (1995) Opiates and alcohol self-administration in animals. J Clin Psychiatry 56(Suppl 7):5–14

    PubMed  Google Scholar 

  • Vacca G, Serra S, Brunetti G, Carai MA, Gessa GL, Colombo G (2002) Boosting effect of morphine on alcohol drinking is suppressed not only by naloxone but also by the cannabinoid CB1 receptor antagonist, SR 141716. Eur J Pharmacol 445:55–59

    PubMed  CAS  Google Scholar 

  • Valjent E, Pages C, Herve D, Girault JA, Caboche J (2004) Addictive and non-addictive drugs induce distinct and specific patterns of ERK activation in mouse brain. Eur J Neurosci 19:1826–1836

    PubMed  Google Scholar 

  • Valjent E, Corbille AG, Bertran-Gonzalez J, Herve D, Girault JA (2006a) Inhibition of ERK pathway or protein synthesis during reexposure to drugs of abuse erases previously learned place preference. Proc Natl Acad Sci U S A 103:2932–2937

    PubMed  CAS  Google Scholar 

  • Valjent E, Corvol JC, Trzaskos JM, Girault JA, Herve D (2006b) Role of the ERK pathway in psychostimulant-induced locomotor sensitization. BMC Neurosci 7:20

    PubMed  Google Scholar 

  • Vanhoutte P, Barnier JV, Guibert B, Pages C, Besson MJ, Hipskind RA, Caboche J (1999) Glutamate induces phosphorylation of Elk-1 and CREB, along with c-fos activation, via an extracellular signal-regulated kinase-dependent pathway in brain slices. Mol Cell Biol 19:136–146

    PubMed  CAS  Google Scholar 

  • Weeks JR, Collins RJ (1976) Changes in morphine self-administration in rats induced by prostaglandin E1 and naloxone. Prostaglandins 12:11–19

    PubMed  CAS  Google Scholar 

  • Woods JH, Downs DA, Carney J (1975) Behavioral functions of narcotic antagonists: response-drug contingencies. Fed Proc 34:1777–1784

    PubMed  CAS  Google Scholar 

  • Woolverton WL (1986) Effects of a D1 and a D2 dopamine antagonist on the self-administration of cocaine and piribedil by rhesus monkeys. Pharmacol Biochem Behav 24:531–535

    PubMed  CAS  Google Scholar 

  • Wu TH, Lin CH (2008) IL-6 mediated alterations on immobile behavior of rats in the forced swim test via ERK1/2 activation in specific brain regions. Behav Brain Res 193:183–191

    PubMed  CAS  Google Scholar 

  • Yang L, Mao L, Chen H, Catavsan M, Kozinn J, Arora A, Liu X, Wang JQ (2006) A signaling mechanism from G alpha q-protein-coupled metabotropic glutamate receptors to gene expression: role of the c-Jun N-terminal kinase pathway. J Neurosci 26:971–980

    PubMed  CAS  Google Scholar 

  • Zghoul T, Abarca C, Sanchis-Segura C, Albrecht U, Schumann G, Spanagel R (2007) Ethanol self-administration and reinstatement of ethanol-seeking behavior in Per1(Brdm1) mutant mice. Psychopharmacology (Berl) 190:13–19

    CAS  Google Scholar 

  • Zhai H, Li Y, Wang X, Lu L (2008) Drug-induced alterations in the extracellular signal-regulated kinase (ERK) signalling pathway: implications for reinforcement and reinstatement. Cell Mol Neurobiol 28:157–172

    PubMed  CAS  Google Scholar 

  • Zhang M, Kelley AE (2002) Intake of saccharin, salt, and ethanol solutions is increased by infusion of a mu opioid agonist into the nucleus accumbens. Psychopharmacology (Berl) 159:415–423

    CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by NIAAA grants AA011605 (CWH), AA014983 (CWH), and AA007573 (Bowles Center for Alcohol Studies Training Grant). The authors would like to thank Michael C Salling for his outstanding experimental assistance.

Author information

Authors and Affiliations

  1. Bowles Center for Alcohol Studies, Department of Psychiatry, University of North Carolina at Chapel Hill, CB #7178, Thurston Bowles Building, Chapel Hill, NC, 27599, USA

    Sara Faccidomo, Joyce Besheer, P. Crystal Stanford & Clyde W. Hodge

Authors
  1. Sara Faccidomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joyce Besheer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Crystal Stanford
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Clyde W. Hodge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Clyde W. Hodge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faccidomo, S., Besheer, J., Stanford, P.C. et al. Increased operant responding for ethanol in male C57BL/6J mice: specific regulation by the ERK1/2, but not JNK, MAP kinase pathway. Psychopharmacology 204, 135–147 (2009). https://doi.org/10.1007/s00213-008-1444-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1444-9

Keywords

Search

Navigation