[en] Repeated ethanol injections lead to a sensitization of its stimulant effects in mice. Some recent results argue against a role for ventral tegmental area (VTA) dopamine neurons in ethanol behavioral sensitization. The aim of the present study was to test whether in vivo ethanol locomotor sensitization correlates with changes in either basal- or ethanol evoked firing rates of dopamine neurons in vitro. Female Swiss mice were daily injected with 2.5 g/kg ethanol (or saline in the control group) for 7 days and their locomotor activity was recorded. At the end of the sensitization procedure, extracellular recordings were made from dopaminergic neurons in midbrain slices from these mice. Significantly higher spontaneous basal firing rates of dopamine neurons were recorded in ethanol-sensitized mice relative to control mice, but without correlations with the behavioral effects. The superfusion of sulpiride, a dopamine D2 antagonist, induced a stronger increase of dopamine neuron firing rates in ethanol-sensitized mice. This shows that the D2 feedback in dopamine neurons is preserved after chronic ethanol administration and argues against a reduced D2 feedback as an explanation for the increased dopamine neuron basal firing rates in ethanol-sensitized mice. Finally, ethanol superfusion (10–100 mM) significantly increased the firing rates of dopamine neurons and this effect
was of higher magnitude in ethanol-sensitized mice. Furthermore, there were significant correlations between such a sensitization of dopamine neuron activity and ethanol behavioral sensitization. These results support the hypothesis that changes in brain dopamine neuron activity contribute to the behavioral sensitization of the stimulant effects of ethanol.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Didone, Vincent ; Université de Liège > Département de Psychologie : cognition et comportement > Psychologie quantitative
Masson, Sébastien
Quoilin, Caroline
Seutin, Vincent ; Université de Liège > Département des sciences biomédicales et précliniques > Pharmacologie
Quertemont, Etienne ; Université de Liège > Département de Psychologie : cognition et comportement > Psychologie quantitative
Language :
English
Title :
Correlation between ethanol behavioral sensitization and midbrain dopamine neuron reactivity to ethanol
Publication date :
2016
Journal title :
Addiction Biology
ISSN :
1355-6215
eISSN :
1369-1600
Publisher :
Blackwell Publishing, Oxford, United Kingdom
Volume :
21
Issue :
2
Pages :
387-396
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Abrahao KP, Souza-Formigoni ML, (2012) Behavioral sensitization to ethanol results in cross-sensitization to MK-801 but not to NMDA administered intra-accumbens. Behav Brain Res 235: 218-224.
Abrahao KP, Quadros IM, Souza-Formigoni ML, (2009) Individual differences to repeated ethanol administration may predict locomotor response to other drugs, and vice versa. Behav Brain Res 197: 404-410.
Abrahao KP, Quadros IM, Souza-Formigoni ML, (2011) Nucleus accumbens dopamine D(1) receptors regulate the expression of ethanol-induced behavioural sensitization. Int J Neuropsychopharmacol 14: 175-185.
Abrahao KP, Quadros IM, Andrade AL, Souza-Formigoni ML, (2012) Accumbal dopamine D2 receptor function is associated with individual variability in ethanol behavioral sensitization. Neuropharmacology 62: 882-889.
Bailey CP, Manley SJ, Watson WP, Wonnacott S, Molleman A, Little HJ, (1998) Chronic ethanol administration alters activity in ventral tegmental area neurons after cessation of withdrawal hyperexcitability. Brain Res 803: 144-152.
Broadbent J, Kampmueller KM, Koonse SA, (2005) Role of dopamine in behavioral sensitization to ethanol in DBA/2J mice. Alcohol 35: 137-148.
Brodie MS, (2002) Increased ethanol excitation of dopaminergic neurons of the ventral tegmental area after chronic ethanol treatment. Alcohol Clin Exp Res 26: 1024-1030.
Brodie MS, Shefner SA, Dunwiddie TV, (1990) Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res 508: 65-69.
Brodie MS, Trifunovic RD, Shefner SA, (1995) Serotonin potentiates ethanol-induced excitation of ventral tegmental area neurons in brain slices from three different rat strains. J Pharmacol Exp Ther 273: 1139-1146.
Camarini R, Marcourakis T, Teodorov E, Yonamine M, Calil HM, (2011) Ethanol-induced sensitization depends preferentially on D1 rather than D2 dopamine receptors. Pharmacol Biochem Behav 98: 173-180.
de Araujo NP, Fukushiro DF, Grassl C, Hipolide DC, Souza-Formigoni ML, Tufik S, Frussa-Filho R, (2009) Ethanol-induced behavioral sensitization is associated with dopamine receptor changes in the mouse olfactory tubercle. Physiol Behav 96: 12-17.
Di Chiara G, Imperato A, (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A 85: 5274-5278.
Diana M, Pistis M, Muntoni A, Rossetti ZL, Gessa G, (1992) Marked decrease of A10 dopamine neuronal firing during ethanol withdrawal syndrome in rats. Eur J Pharmacol 221: 403-404.
Diana M, Pistis M, Carboni S, Gessa GL, Rossetti ZL, (1993) Profound decrement of mesolimbic dopaminergic neuronal activity during ethanol withdrawal syndrome in rats: Electrophysiological and biochemical evidence. Proc Natl Acad Sci U S A 90: 7966-7969.
Diana M, Pistis M, Muntoni A, Gessa G, (1996) Mesolimbic dopaminergic reduction outlasts ethanol withdrawal syndrome: Evidence of protracted abstinence. Neuroscience 71: 411-415.
Didone V, Quoilin C, Tirelli E, Quertemont E, (2008) Parametric analysis of the development and expression of ethanol-induced behavioral sensitization in female Swiss mice: Effects of dose, injection schedule, and test context. Psychopharmacology (Berl) 201: 249-260.
Ding ZM, Rodd ZA, Engleman EA, McBride WJ, (2009) Sensitization of ventral tegmental area dopamine neurons to the stimulating effects of ethanol. Alcohol Clin Exp Res 33: 1571-1581.
Engleman EA, McBride WJ, Li TK, Lumeng L, Murphy JM, (2003) Ethanol drinking experience attenuates (-)sulpiride-induced increases in extracellular dopamine levels in the nucleus accumbens of alcohol-preferring (P) rats. Alcohol Clin Exp Res 27: 424-431.
Gessa GL, Muntoni F, Collu M, Vargiu L, Mereu G, (1985) Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res 348: 201-203.
Harrison SJ, Nobrega JN, (2009) A functional role for the dopamine D3 receptor in the induction and expression of behavioural sensitization to ethanol in mice. Psychopharmacology (Berl) 207: 47-56.
Hauser SR, Ding ZM, Getachew B, Toalston JE, Oster SM, McBride WJ, Rodd ZA, (2011) The posterior ventral tegmental area mediates alcohol-seeking behavior in alcohol-preferring rats. J Pharmacol Exp Ther 336: 857-865.
Johnson SW, North RA, (1992) Two types of neurone in the rat ventral tegmental area and their synaptic inputs. J Physiol 450: 455-468.
Kalivas PW, Duffy P, (1990) Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens. Synapse 5: 48-58.
Legastelois R, Botia B, Coune F, Jeanblanc J, Naassila M, (2014) Deciphering the relationship between vulnerability to ethanol-induced behavioral sensitization and ethanol consumption in outbred mice. Addict Biol 19: 210-224.
Morzorati SL, Marunde RL, Downey D, (2010) Limited access to ethanol increases the number of spontaneously active dopamine neurons in the posterior ventral tegmental area of nondependent P rats. Alcohol 44: 257-264.
Nestby P, Vanderschuren LJ, De Vries TJ, Hogenboom F, Wardeh G, Mulder AH, Schoffelmeer AN, (1997) Ethanol, like psychostimulants and morphine, causes long-lasting hyperreactivity of dopamine and acetylcholine neurons of rat nucleus accumbens: Possible role in behavioural sensitization. Psychopharmacology (Berl) 133: 69-76.
Nestby P, Vanderschuren LJ, De Vries TJ, Mulder AH, Wardeh G, Hogenboom F, Schoffelmeer AN, (1999) Unrestricted free-choice ethanol self-administration in rats causes long-term neuroadaptations in the nucleus accumbens and caudate putamen. Psychopharmacology (Berl) 141: 307-314.
Onali P, Olianas MC, Bunse B, (1988) Evidence that adenosine A2 and dopamine autoreceptors antagonistically regulate tyrosine hydroxylase activity in rat striatal synaptosomes. Brain Res 456: 302-309.
Perra S, Clements MA, Bernier BE, Morikawa H, (2011) In vivo ethanol experience increases D(2) autoinhibition in the ventral tegmental area. Neuropsychopharmacology 36: 993-1002.
Quadros IM, Nobrega JN, Hipolide DC, Souza-Formigoni ML, (2005) Increased brain dopamine D4-like binding after chronic ethanol is not associated with behavioral sensitization in mice. Alcohol 37: 99-104.
Quoilin C, Didone V, Tirelli E, Quertemont E, (2012) Developmental differences in ethanol-induced sensitization using postweanling, adolescent, and adult Swiss mice. Psychopharmacology (Berl) 219: 1165-1177.
Robinson TE, Berridge KC, (1993) The neural basis of drug craving: An incentive-sensitization theory of addiction. Brain Research Reviews 18: 247-291.
Rodd ZA, Bell RL, McQueen VK, Davids MR, Hsu CC, Murphy JM, Li TK, Lumeng L, McBride WJ, (2005) Chronic ethanol drinking by alcohol-preferring rats increases the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol. Alcohol Clin Exp Res 29: 358-366.
Roeper J, (2013) Dissecting the diversity of midbrain dopamine neurons. Trends Neurosci 36: 336-342.
Scuvee-Moreau J, Liegeois JF, Massotte L, Seutin V, (2002) Methyl-laudanosine: A new pharmacological tool to investigate the function of small-conductance Ca(2+)-activated K(+) channels. J Pharmacol Exp Ther 302: 1176-1183.
Seutin V, Scuvee-Moreau J, Giesbers I, Massotte L, Dresse A, (1990) Effect of BHT 920 on monoaminergic neurons of the rat brain: An electrophysiological in vivo and in vitro study. Naunyn Schmiedebergs Arch Pharmacol 342: 502-507.
Seutin V, Scuvee-Moreau J, Dresse A, (1997) Evidence for a non-GABAergic action of quaternary salts of bicuculline on dopaminergic neurones. Neuropharmacology 36: 1653-1657.
Shen RY, (2003) Ethanol withdrawal reduces the number of spontaneously active ventral tegmental area dopamine neurons in conscious animals. J Pharmacol Exp Ther 307: 566-572.
Shen RY, Chiodo LA, (1993) Acute withdrawal after repeated ethanol treatment reduces the number of spontaneously active dopaminergic neurons in the ventral tegmental area. Brain Res 622: 289-293.
Smith AD, Weiss F, (1999) Ethanol exposure differentially alters central monoamine neurotransmission in alcohol-preferring versus -nonpreferring rats. J Pharmacol Exp Ther 288: 1223-1228.
Souza-Formigoni ML, De Lucca EM, Hipolide DC, Enns SC, Oliveira MG, Nobrega JN, (1999) Sensitization to ethanol's stimulant effect is associated with region-specific increases in brain D2 receptor binding. Psychopharmacology (Berl) 146: 262-267.
Thielen RJ, Engleman EA, Rodd ZA, Murphy JM, Lumeng L, Li TK, McBride WJ, (2004) Ethanol drinking and deprivation alter dopaminergic and serotonergic function in the nucleus accumbens of alcohol-preferring rats. J Pharmacol Exp Ther 309: 216-225.
Ungless MA, Grace AA, (2012) Are you or aren't you? Challenges associated with physiologically identifying dopamine neurons. Trends Neurosci 35: 422-430.
Vanderschuren LJ, Kalivas PW, (2000) Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: A critical review of preclinical studies. Psychopharmacology (Berl) 151: 99-120.
Wise RA, Bozarth MA, (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94: 469-492.
Zapata A, Gonzales RA, Shippenberg TS, (2006) Repeated ethanol intoxication induces behavioral sensitization in the absence of a sensitized accumbens dopamine response in C57BL/6J and DBA/2J mice. Neuropsychopharmacology 31: 396-405.
