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Differential involvement of anxiety and novelty preference levels on oral ethanol consumption in rats

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Abstract

Rationale

Drug addiction is defined as a recurring cycle of intoxication, abstinence and relapse. The behavioural trait of novelty seeking is frequently observed in alcohol abusers. Moreover, converging evidence indicates that anxious individuals are also predisposed to alcohol abuse.

Objectives

We have analyzed the respective implication of those two behavioural factors on vulnerability to ethanol intake on rats in situations designed to reflect drug intoxication and relapse phases in humans.

Methods

In a general population of Wistar rats, animals were tested in both the light/dark box and the novelty preference tests. Ethanol consumption was measured in a two-bottle free-choice procedure across three successive procedures. Animals were first exposed to increasing concentrations of ethanol (2, 4, 6, 8, 10, 12 % for 8 days at each concentration). Then, the concentration of the solution was diminished from 12 to 6 %. Finally, all rats were re-exposed to 6 % ethanol after 12 days of ethanol deprivation.

Results

Novelty preference predicted the amount of ethanol consumed across all phases. In contrast, anxiety was associated with a quicker recovery of ethanol consumption after the concentration drop and a greater increase in ethanol consumption after deprivation.

Conclusions

Novelty seeking and anxiety are both but differentially implicated in predisposition to ethanol abuse. Whereas novelty seeking is related to the amount of ethanol consumed, anxiety is associated to higher ethanol consumption when ethanol concentration is decreased or after ethanol deprivation.

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References

  • Badiani A, Belin D, Epstein D, Calu D, Shaham Y (2011) Opiate versus psychostimulant addiction: the differences do matter. Nat Rev Neurosci 12(11):685–700

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bahi A (2013) Individual differences in elevated plus-maze exploration predicted higher ethanol consumption and preference in outbred mice. Pharmacol Biochem Behav 105:83–88

    Article  CAS  PubMed  Google Scholar 

  • Bardo MT, Donohew RL, Harrington NG (1996) Psychobiology of novelty seeking and drug seeking behaviour. Behav Brain Res 77:23–43

    Article  CAS  PubMed  Google Scholar 

  • Bardo MT, Neisewander JL, Kelly TH (2013) Individual differences and social influences on the neurobehavioral pharmacology of abused drugs. Pharmacol Rev 65(1):255–290

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Becker HC, Flaherty CF (1983) Chlordiazepoxide and ethanol additively reduce gustatory negative contrast. Psychopharmacol (Berl) 80(1):35–37

    Article  CAS  Google Scholar 

  • Becker HC, Hale RL (1991) RO15-4513 antagonizes the anxiolytic effects of ethanol in a nonshock conflict task at doses devoid of anxiogenic activity. Pharmacol Biochem Behav 39(3):803–807

    Article  CAS  PubMed  Google Scholar 

  • Belin D, Berson N, Balado E, Piazza PV, Deroche-Gamonet V (2011) High-novelty-preference rats are predisposed to compulsive cocaine self-administration. Neuropsychopharmacology 36(3):569–579

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bienkowski P, Koros E, Kostowski W (2001) Novelty-seeking behaviour and operant oral ethanol self-administration in Wistar rats. Alcohol Alcohol 36(6):525–528

    Article  CAS  PubMed  Google Scholar 

  • Bisaga A, Kostowski W (1993) Individual behavioral differences and ethanol consumption in Wistar rats. Physiol Behav 54(6):1125–1131

    Article  CAS  PubMed  Google Scholar 

  • Blatt SL, Takahashi RN (1999) Experimental anxiety and the reinforcing effects of ethanol in rats. Braz J Med Biol Res 32(4):457–461

    Article  CAS  PubMed  Google Scholar 

  • Cloninger CR (1987) Neurogenetic adaptive mechanisms in alcoholism. Science 236(4800):410–416

    Article  CAS  PubMed  Google Scholar 

  • Cloninger CR, Svrakic DM, Przybeck TR (1993) A psychobiological model of temperament and character. Arch Gen Psychiatry 50(12):975–990

    Article  CAS  PubMed  Google Scholar 

  • Conger J (1956) Alcoholism: theory, problem and challenge. II. Reinforcement theory and the dynamics of alcoholism. Q J Stud Alcohol 17:296–305

    CAS  PubMed  Google Scholar 

  • Correia D, Ribeiro AF, Brunialti Godard AL, Boerngen-Lacerda R (2009) Trait anxiety and ethanol: anxiolysis in high-anxiety mice and no relation to intake behavior in an addiction model. Prog Neuropsychopharmacol Biol Psychiatry 33(5):880–888

    Article  CAS  PubMed  Google Scholar 

  • Da Silva GE, Ramos A, Takahashi RN (2004) Comparison of voluntary ethanol intake by two pairs of rat lines used as genetic models of anxiety. Braz J Med Biol Res 37(10):1511–1517

    Article  PubMed  Google Scholar 

  • Dilleen R, Pelloux Y, Mar AC, Molander A, Robbins TW, Everitt BJ, Dalley JW, Belin D (2012) High anxiety is a predisposing endophenotype for loss of control over cocaine, but not heroin, self-administration in rats. Psychopharmacol (Berl) 222(1):89–97

    Article  CAS  Google Scholar 

  • Ersche KD, Turton AJ, Pradhan S, Bullmore ET, Robbins TW (2010) Drug addiction endophenotypes: impulsive versus sensation-seeking personality traits. Biol Psychiatry 68(8):770–773

    Article  PubMed Central  PubMed  Google Scholar 

  • Ettenberg A, Geist TD (1991) Animal model for investigating the anxiogenic effects of self-administered cocaine. Psychopharmacol (Berl) 103(4):455–461

    Article  CAS  Google Scholar 

  • Exner M, Clark D (1993) Behaviour in the novel environment predicts responsiveness to d-amphetamine in the rat: a multivariate approach. Behav Pharmacol 4(1):47–56

    Article  CAS  PubMed  Google Scholar 

  • Fahlke C, Hard E, Eriksson C, Engel J, Hansen S (1995) Amphetamine-induced hyperactivity: differences between rats with high or low preference for alcohol. Alcohol 12:363–367

    Article  CAS  PubMed  Google Scholar 

  • Flaherty CF, Lombardi BR, Wrightson J, Deptula D (1980) Conditions under which chlordiazepoxide influences gustatory contrast. Psychopharmacology 67(3):269–277

    Article  CAS  PubMed  Google Scholar 

  • Gingras MA, Cools AR (1995) Differential ethanol intake in high and low responders to novelty. Behav Pharmacol 6(7):718–723

    Article  CAS  PubMed  Google Scholar 

  • Hayton SJ, Mahoney MK, Olmstead MC (2012) Behavioral traits predicting alcohol drinking in outbred rats: an investigation of anxiety, novelty seeking, and cognitive flexibility. Alcohol Clin Exp Res 36(4):594–603

    Article  PubMed  Google Scholar 

  • Henniger MS, Spanagel R, Wigger A, Landgraf R, Hölter SM (2002) Alcohol self-administration in two rat lines selectively bred for extremes in anxiety-related behavior. Neuropsychopharmacology 26(6):729–736

    Article  CAS  PubMed  Google Scholar 

  • Homberg JR, van den Akker M, Raasø HS, Wardeh G, Binnekade R, Schoffelmeer AN, de Vries TJ (2002) Enhanced motivation to self-administer cocaine is predicted by self-grooming behaviour and relates to dopamine release in the rat medial prefrontal cortex and amygdala. Eur J Neurosci 15(9):1542–1550

    Article  PubMed  Google Scholar 

  • Izídio GS, Ramos A (2007) Positive association between ethanol consumption and anxiety-related behaviors in two selected rat lines. Alcohol 41(7):517–524

    Article  PubMed  Google Scholar 

  • Karatayev O, Barson JR, Carr AJ, Baylan J, Chen YW, Leibowitz SF (2010) Predictors of ethanol consumption in adult Sprague-Dawley rats: relation to hypothalamic peptides that stimulate ethanol intake. Alcohol 44(4):323–334

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Khantzian EJ (1985) The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry 142(11):1259–1264

    Article  CAS  PubMed  Google Scholar 

  • Klebaur JE, Bardo MT (1999) Individual differences in novelty seeking on the playground maze predict amphetamine-conditioned place preference. Pharmacol Biochem Behav 63:131–136

    Article  CAS  PubMed  Google Scholar 

  • Koob GF (2009) Neurobiological substrates for the dark side of compulsivity in addiction. Neuropharmacology 56(Suppl 1):18–31

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Koob GF (2013) Theoretical frameworks and mechanistic aspects of alcohol addiction: alcohol addiction as a reward deficit disorder. Curr Topics Behav Neurosci 13:3–30

    Article  Google Scholar 

  • Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278(5335):52–58

    Article  CAS  PubMed  Google Scholar 

  • Koros E, Piasecki J, Kostowski W, Bienkowski P (1998) Saccharin drinking rather than open field behaviour predicts initial ethanol acceptance in Wistar rats. Alcohol Alcohol 33(2):131–140

    Article  CAS  PubMed  Google Scholar 

  • Kushner MG, Maurer E, Menary K, Thuras P (2011) Vulnerability to the rapid (“telescoped”) development of alcohol dependence in individuals with anxiety disorder. J Stud Alcohol Drugs 72(6):1019–1027

    Article  PubMed Central  PubMed  Google Scholar 

  • Langen B, Fink H (2004) Anxiety as a predictor of alcohol preference in rats? Prog Neuropsychopharmacol Biol Psychiatry 28(6):961–968

    Article  CAS  PubMed  Google Scholar 

  • Leshner AI (1997) Addiction is a brain disease, and it matters. Science 278(5335):45–47

    Article  CAS  PubMed  Google Scholar 

  • Manzo L, Gómez MA, Callejas-Aguilera JE, Donaire R, Sabariego M, Fernández-Teruel A, Cañete A, Blázquez G, Papini MR, Torres C (2014) Relationship between ethanol preference and sensation/novelty seeking. Physiol Behav 133:53–60

    Article  CAS  PubMed  Google Scholar 

  • Marquenie LA, Schadé A, van Balkom AJ, Comijs HC, de Graaf R, Vollebergh W, van Dyck R, van den Brink W (2007) Origin of the comorbidity of anxiety disorders and alcohol dependence: findings of a general population study. Eur Addict Res 13(1):39–49

    Article  PubMed  Google Scholar 

  • Merikangas KR, Mehta RL, Molnar BE, Walters EE, Swendsen JD, Aguilar-Gaziola S, Bijl R, Borges G, Caraveo-Anduaga JJ, DeWit DJ, Kolody B, Vega WA, Wittchen HU, Kessler RC (1998) Comorbidity of substance use disorders with mood and anxiety disorders: results of the International Consortium in Psychiatric Epidemiology. Addict Behav 23(6):893–907

    Article  CAS  PubMed  Google Scholar 

  • Meszaros K, Lenzinger E, Hornik K, Füreder T, Willinger U, Fischer G, Schönbeck G, Aschauer HN (1999) The Tridimensional Personality Questionnaire as a predictor of relapse in detoxified alcohol dependents. The European Fluvoxamine in Alcoholism Study Group. Alcohol Clin Exp Res 23(3):483–486

    Article  CAS  PubMed  Google Scholar 

  • Misslin R, Herzog F, Koch B, Ropartz P (1982) Effects of isolation, handling and novelty on the pituitary–adrenal response in the mouse. Psychoneuroendocrinology 7(2–3):217–221

    Article  CAS  PubMed  Google Scholar 

  • Nadal R, Armario A, Janak PH (2002) Positive relationship between activity in a novel environment and operant ethanol self-administration in rats. Psychopharmacol (Berl) 162(3):333–338

    Article  CAS  Google Scholar 

  • Pelloux Y, Costentin J, Duterte-Boucher D (2004) Differential effects of novelty exposure on place preference conditioning to amphetamine and its oral consumption. Psychopharmacol (Berl) 171(3):277–285

    Article  CAS  Google Scholar 

  • Pelloux Y, Costentin J, Duterte-Boucher D (2006) Novelty preference predicts place preference conditioning to morphine and its oral consumption in rats. Pharmacol Biochem Behav 84(1):43–50

    Article  CAS  PubMed  Google Scholar 

  • Pelloux Y, Costentin J, Duterte-Boucher D (2009) Anxiety increases the place conditioning induced by cocaine in rats. Behav Brain Res 197(2):311–316

    Article  CAS  PubMed  Google Scholar 

  • Robinet PM, Rowlett JK, Bardo MT (1998) Individual differences in novelty-induced activity and the rewarding effects of novelty and amphetamine in rats. Behav Process 44:1–9

    Article  CAS  Google Scholar 

  • Rounsaville BJ, Anton SF, Carroll K, Budde D, Prusoff BA, Gawin F (1991) Psychiatric diagnoses of treatment-seeking cocaine abusers. Arch Gen Psychiatry 48(1):43–51

    Article  CAS  PubMed  Google Scholar 

  • Sandbak T, Murison R (2001) Behavioural responses to elevated plus-maze and defensive burying testing: effects on subsequent ethanol intake and effect of ethanol on retention of the burying response. Alcohol Alcohol 36(1):48–58

    Article  CAS  PubMed  Google Scholar 

  • Sartor CE, Lynskey MT, Heath AC, Jacob T, True W (2007) The role of childhood risk factors in initiation of alcohol use and progression to alcohol dependence. Addiction 102(2):216–225

    Article  PubMed  Google Scholar 

  • Spanagel R (2000) Recent animal models of alcoholism. Alcohol Res Health 24(2):124–131

    CAS  PubMed  Google Scholar 

  • Spanagel R, Montkowski A, Allingham K, Stöhr T, Shoaib M, Holsboer F, Landgraf R (1995) Anxiety: a potential predictor of vulnerability to the initiation of ethanol self-administration in rats. Psychopharmacol (Berl) 122(4):369–373

    Article  CAS  Google Scholar 

  • Verendeev A, Riley AL (2013) The role of the aversive effects of drugs in self-administration: assessing the balance of reward and aversion in drug-taking behavior. Behav Pharmacol 24(5–6):363–374

    Article  CAS  PubMed  Google Scholar 

  • Vidal-Infer A, Arenas MC, Daza-Losada M, Aguilar MA, Miñarro J, Rodríguez-Arias M (2012) High novelty-seeking predicts greater sensitivity to the conditioned rewarding effects of cocaine. Pharmacol Biochem Behav 102(1):124–132

    Article  CAS  PubMed  Google Scholar 

  • Walker QD, Schramm-Sapyta NL, Caster JM, Waller ST, Brooks MP, Kuhn CM (2009) Novelty-induced locomotion is positively associated with cocaine ingestion in adolescent rats; anxiety is correlated in adults. Pharmacol Biochem Behav 91(3):398–408

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Willinger U, Lenzinger E, Hornik K, Fischer G, Schönbeck G, Aschauer HN, Meszaros K (2002) European fluvoxamine in alcoholism study group. Anxiety as a predictor of relapse in detoxified alcohol-dependent patients. Alcohol Alcohol 37(6):609–612

    Article  PubMed  Google Scholar 

  • Woicik PA, Stewart SH, Pihl RO, Conrod PJ (2009) The Substance Use Risk Profile Scale: a scale measuring traits linked to reinforcement-specific substance use profiles. Addict Behav 34(12):1042–1055

    Article  PubMed  Google Scholar 

  • Zheng X, Ke X, Tan B, Luo X, Xu W, Yang X, Sui N (2003) Susceptibility to morphine place conditioning: relationship with stress-induced locomotion and novelty-seeking behavior in juvenile and adult rats. Pharmacol Biochem Behav 75(4):929–935

    Article  CAS  PubMed  Google Scholar 

  • Zinberg, Norman (1986). Drug, set, and setting: the basis for controlled intoxicant use. Yale University Press. pp. x-xi

  • Zuckerman M (1996) Sensation seeking. In: Costello CG (ed) Personality characteristics of the personality disordered. Wiley, New York, pp 289–316

    Google Scholar 

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Acknowledgements

This work was supported by grants from MILDT/INSERM (contract no. 4TX10H) and Conseil Régional de Haute Normandie.

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Correspondence to Dominique Duterte-Boucher.

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Figure 5

Correlation between the time spent in the novel compartment during the novelty preference test and ethanol consumption expressed as ethanol intake (g/kg/day; left panel) or ethanol ratio (right panel) during the progressive increase of the ethanol concentration for the 8, 10 and 12% of ethanol concentration. N = 50 rats. (GIF 266 kb)

High resolution image (TIFF 1915 kb)

Figure 6

Correlation between the time spent in the novel compartment during the novelty preference test and ethanol consumption expressed as ethanol intake (g/kg/day; left panels) or ethanol ratio (right panels). The upper panels show the correlation between the time spent in the novel compartment and ethanol consumption during the whole 20-day period of the concentration drop from 12% to 6% (w/v). The bottom panels show the correlations between the time spent in the novel compartment and ethanol consumption during the first 2-day period (light grey circle) or during the second 2-day period (dark grey circle) of re-exposure following a 12-day abstinence period. N = 50 rats. (GIF 231 kb)

High resolution image (TIFF 1667 kb)

Figure 7

Correlation between the time spent in the light compartment of the light/dark box and ethanol consumption expressed as ethanol intake (g/kg/day; left panel) or ethanol ratio (right panel) during the 4-day period before (grey circle) or after (black circle) the concentration drop from 12% to 6% (w/v).. N = 50 rats. (GIF 285 kb)

High resolution image (TIFF 153 kb)

Figure 8

Correlation between the time spent in the light compartment of the light/dark box and ethanol consumption expressed as ethanol intake (g/kg/day; left upper panel) or ethanol ratio (right upper panel) during the 2-day period before (grey circle) or after (black circle) a 12-day abstinence period. The bottom panels shows the correlations between the time spent in the light compartment and the difference in ethanol intake (g/kg/d) (left panel) or the difference in ethanol ratio (%) (right panel) after and before the 12-day abstinence period. N = 50 rats. (GIF 201 kb)

High resolution image (TIFF 1429 kb)

Figure 9

Sucrose intake of a 4% sucrose solution of Low Novelty Seekers (LNS) and High Novelty Seekers (HNS), before (pre-shift) and after (post-shift) exposure to a 16% sucrose solution. Mean ± SEM of 18 animals per group. Differences in 4% sucrose consumption, before and after negative contrast: p<0.05: * (Fisher's LSD test). (GIF 1 kb)

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Pelloux, Y., Costentin, J. & Duterte-Boucher, D. Differential involvement of anxiety and novelty preference levels on oral ethanol consumption in rats. Psychopharmacology 232, 2711–2721 (2015). https://doi.org/10.1007/s00213-015-3910-5

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  • DOI: https://doi.org/10.1007/s00213-015-3910-5

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