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Non-Human Primate Models of Alcohol-Related Phenotypes: The Influence of Genetic and Environmental Factors

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Behavioral Neurobiology of Alcohol Addiction

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 13))

Abstract

Because of their complex social structures, behaviors, and genetic similarities to humans, nonhuman primates are useful for studying how genetic factors influence alcohol consumption. The neurobiological systems that influence addiction vulnerability may do so by acting on alcohol response, reward pathways, behavioral dyscontrol, and vulnerability to stress and anxiety. Rhesus macaques show individual differences in alcohol response and temperament, and such differences are influenced by genetic variants that are similar functionally to those present in humans. Genes at which variation moderates these phenotypes include those encoding monoamine oxidase A (MAOA-LPR), the serotonin transporter (HTTLPR), corticotropin releasing hormone (CRH-248C/T and -2232 C/G), Neuropeptide Y (NPY-1002 T/G), and the μ-opioid receptor (OPRM1 C77G). These provide opportunities for modeling how genetic and environmental factors (i.e., stress, individual’s sex, or alcohol exposure) interact to influence alcohol consumption. Studies in primates may also reveal selective factors have driven maintenance or fixation of alleles that increase risk for alcohol use disorders in modern humans.

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References

  • Anton RF, Oroszi G, O'Malley S, Couper D, Swift R, Pettinati H, Goldman D (2008) An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry 65(2):135–144

    Google Scholar 

  • Badia-Elder NE, Stewart RB, Powrozek TA, Roy KF, Murphy JM, Li TK (2001) Effect of neuropeptide Y (NPY) on oral ethanol intake in Wistar, alcohol- preferring (P), and -nonpreferring (NP) rats. Alcohol Clin Exp Res 25(3):386–390

    CAS  PubMed  Google Scholar 

  • Badia-Elder NE, Stewart RB, Powrozek TA, Murphy JM, Li TK (2003) Effects of neuropeptide Y on sucrose and ethanol intake and on anxiety-like behavior in high alcohol drinking (HAD) and low alcohol drinking (LAD) rats. Alcohol Clin Exp Res 27(6):894–899

    CAS  PubMed  Google Scholar 

  • Baerwald CG, Mok CC, Fife MS, Tickly M, Lau CS, Wordsworth BP, Ollier B, Panayi GS, Lanchbury JS (1999) Distribution of corticotropin-releasing hormone promoter polymorphism in different ethnic groups: evidence for natural selection in human populations. Immunogenetics 49:894–899

    CAS  PubMed  Google Scholar 

  • Barr CS, Goldman D (2006) Nonhuman primate models of inheritance of vulnerability to alcohol abuse and addiction. Addiction Biol 11:374–385

    Google Scholar 

  • Barr CS, Newman TK, Becker ML, Champoux M, Lesch K-P, Suomi SJ, Goldman D, Higley JD (2003a) Serotonin transporter gene variation is associated with alcohol sensitivity in rhesus macaques exposed to early-life stress. Alc Clin Exp Res 27:812–817

    CAS  Google Scholar 

  • Barr CS, Newman TK, Becker ML, Parker CC, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2003b) The utility of the non-human primate; model for studying gene by environment interactions in behavioral research. Genes Brain Behav 2:336–340

    CAS  PubMed  Google Scholar 

  • Barr CS, Newman TK, Lindell S, Shannon C, Champoux M, Lesch KP, Suomi SJ, Goldman D, Higley JD (2004a) Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates. Arch Gen Psychiatry 61:1146–1152

    CAS  PubMed  Google Scholar 

  • Barr CS, Newman TK, Schwandt M, Shannon C, Dvoskin RL, Lindell SG, Taubman H, Thompson B, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2004b) Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques. Proc Natl Acad Sci USA 101:12358–12363

    CAS  PubMed  Google Scholar 

  • Barr CS, Newman TK, Shannon C, Parker C, Dvoskin RL, Becker ML, Schwandt M, Champoux M, Lesch KP, Goldman D, Suomi SJ, Higley JD (2004c) Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques. Biol Psychiatry 55:733–738

    CAS  PubMed  Google Scholar 

  • Barr CS, Schwandt M, Newman TK, Higley JD (2004d) The use of adolescent nonhuman primates to model human alcohol intake: neurobiological, genetic and environmental variables. Ann. NY Acad. Sci 1021:221–233

    CAS  PubMed  Google Scholar 

  • Barr CS, Newman TK, Lindell S, Becker ML, Shannon CS, Champoux C, Suomi SJ, Higley JD (2004e) Early experience and sex interact to influence LHPA-axis function following both acute and chronic alcohol administration in Rhesus Macaques (Macaca mulatta). Alcohol Clin Exp Res 28(7):1–5

    Google Scholar 

  • Barr CS, Schwandt ML, Lindell SG, Chen SA, Suomi SJ, Goldman D, Heilig M, Higley JD (2007) Mu opioid receptor gene variation is associated with alcohol response and consumption in rhesus monkeys. Arch Gen Psychiatry 64:369–376

    CAS  PubMed  Google Scholar 

  • Barr CS, Schwandt ML, Lindell SG, Higley JD, Maestripieri D, Goldman D, Suomi SJ, Heilig M (2008a) A functional OPRM1 variant is associated with attachment behavior in infant rhesus macaques. Proc Natl Acad Sci 105:5277–5281

    CAS  PubMed  Google Scholar 

  • Barr CS, Dvoskin RL, Yuan Q, Lipsky RH, Gupte M, Hu X, Zhou Z, Schwandt ML, Lindell SG, McKee M, Becker ML, Kling MA, Gold PW, Higley JD, Heilig M, Suomi SJ, Goldman D (2008b) CRH haplotype as a factor influencing cerebrospinal fluid levels of corticotropin-releasing hormone, hypothalamic-pituitary-adrenal axis activity, temperament, and alcohol consumption in rhesus macaques. Arch Gen Psychiatry 65(8):934–944

    CAS  PubMed Central  PubMed  Google Scholar 

  • Barr CS, Dvoskin RL, Gupte M, Sommer W, Sun H, Schwandt ML, Lindell SG, Kasckow JW, Suomi SJ, Goldman D, Higley HD, Heilig M (2009) Functional CRH promoter variation drives stress-induced alcohol consumption in primates. Proc Natl Acad Sci 106:14593–14598

    CAS  PubMed  Google Scholar 

  • Barr CS, Chen SA, Schwandt ML, Lindell SG, Sun H, Suomi SJ, Heilig M (2010) Suppression of alcohol preference by naltrexone in the rhesus macaque: a critical role of genetic variation at the micro-opioid receptor gene locus. Biol Psychiatry 67:78–80

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bennett AJ, Lesch K-P, Heils A, Long JC, Lorenz JG, Shoaf SE, Champoux M, Suomi SJ, Linnoila MV, Higley JD (2002) Early experience and serotonin transporter gene variation interact to influence primate CNS function. Mol Psychiatry 7:118–122

    CAS  PubMed  Google Scholar 

  • Bethea CL, Streicher JM, Coleman K, Pau FKY, Moessner R, Cameron JL (2004) Anxious behavior and fenfluramine-induced prolactin secretion in young rhesus macaques with different alleles of the serotonin reuptake transporter polymorphism (5HTTLPR). Behav Genet 34:295–307

    PubMed  Google Scholar 

  • Bethea CL, Streicher JM, Mirkes SJ, Sanchez RL, Reddy AP, Cameron JL (2006) Serotonin-related gene expression in female monkeys with individual sensitivity to stress. Neuroscience 132:151–166

    Google Scholar 

  • Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M (2008) Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry 63:146–151

    CAS  PubMed  Google Scholar 

  • Bradwejn J, Kosycki D, Deutetre-Couteax A, Bourin M, Palmour RM, Ervin FR (1992) The cholecystokinin hypothesis of panic and anxiety disorders: a review. J Psychopharm 6:345–351

    CAS  Google Scholar 

  • Cale EM, Lilienfeld SO (2002) Sex differences in psychopathy and antisocial personality disorder: a review and integration. Clin Psychol Rev 22:1179–1207

    PubMed  Google Scholar 

  • Capitanio JP, Widaman KF (2005) Confirmatory factor analysis of personality structure in adult male rhesus monkeys (Macaca mulatta). Am J Primatol 65:289–294

    PubMed  Google Scholar 

  • Caspi A, Moffitt TE (2006) Gene-environment interactions in psychiatry: joining forces with neuroscience. Nat Rev Neurosci 7(7):583–590

    CAS  PubMed  Google Scholar 

  • Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R (2002) Role of genotype in the cycle of violence in maltreated children. Science 297:851–854

    CAS  PubMed  Google Scholar 

  • Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389

    CAS  PubMed  Google Scholar 

  • Caspi A, Hariri AR, Holmes A, Uher R, Mofitt TE (2010) Genetic sensitivity to the environment; the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 167(5):509–527

    PubMed Central  PubMed  Google Scholar 

  • Chamove AS, Rosenblum LA, Harlow HF (1973) Monkeys (Macaca mulatta) raised only with peers. Animal Behav 21:316–325

    CAS  Google Scholar 

  • Champoux M, Bennett A, Shannon C, Higley JD, Lesch KP, Suomi SJ (2002) Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Mol Psychiatry 7:1058–1063

    CAS  PubMed  Google Scholar 

  • Chong RY, Oswald L, Yang X, Uhart M, Lin PI, Wand GS (2006) The mu-opioid receptor polymorphism A118G predicts cortisol responses to naloxone and stress. Neuropsychopharmacology 31:204–211

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Contini V, Marques FZ, Farcia CE, Hutz MH, Bau CH (2006) MAOA-uVNTR polymorphism in a Brazilian sample; further support for the association with impulsive behaviors and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 141:305–308

    Google Scholar 

  • Copeland WE, Sun H, Costello EJ, Angold A, Heilig MA, Barr CS (2011) Child–opioid receptor gene variant influences parent-child relations. Neuropsychopharmacololgy 36(6):1165–1170

    Google Scholar 

  • Dudley R (2002) Fermenting fruit and the historical ecology of ethanol ingestion: is alcoholism in modern humans an evolutionary hangover? Addiction 97:381–388

    PubMed  Google Scholar 

  • Egli M (2005) Can experimental paradigms and animal models be used to discover clinically effective medications for alcoholism? Addiction Biol 10:309–319

    CAS  Google Scholar 

  • Eme RF (2007) Sex differences in child-onset, life-course-persistent conduct disorder. A review of biological influences. Clin Psychol Rev 27:607–627

    PubMed  Google Scholar 

  • Ervin FR, Palmour RM, Young SN, Guzman-Flores C, Juarez J (1990) Voluntary consumption of beverage alcohol by vervet monkeys, population screening, descriptive behavior and biochemical measures. Pharmacol Biochem Behav 36:367–373

    CAS  PubMed  Google Scholar 

  • Fairbanks LA, Newman TK, Bailey JN, Jorgensen MJ, Breidenthal SE, Ophoff RA, Comuzzie AG, Marin LJ, Rogers J (2004) Genetic contributions to social impulsivity and aggressiveness in vervet monkeys. Biol Psychiatry 55:642–647

    PubMed  Google Scholar 

  • Fiskerstrand CE, Lovejoy EA, Quinn JP (1999) An intronic polymorphic domain often associated with susceptibility to affective disorders has allele dependent differential enhancer activity in embryonic stem cells. FEBS Lett 458:171–174

    CAS  PubMed  Google Scholar 

  • Freeman HD, Gosling SD (2010) Personality in Nonhuman primates: a review and evaluation of past research. Am J Primatol 71:1–19

    Google Scholar 

  • Gold PW, Chrousos GP (2002) Organization of the stress system and its dysregulation in melancholic and atypical depression: high vs low CRH/NE states. Mol Psychiatry 7:254–275

    CAS  PubMed  Google Scholar 

  • Goldman D, Barr CS (2002) Restoring the addicted brain. N Engl J Med 347:843–845

    PubMed  Google Scholar 

  • Goldman D, Oroszi G, Ducci F (2005) The genetics of addictions: uncovering the genes. Nat Rev Genet 6:521–532

    CAS  PubMed  Google Scholar 

  • Grant KA, Bennett AJ (2003) Advances in nonhuman primate alcohol abuse and alcoholism research. Pharmacol Ther 100:235–255

    CAS  PubMed  Google Scholar 

  • Hansson AC, Cippitelli A, Sommer WH, Fedeli A, Bjork K, Soverchia L, Terasmaa A, Massi M, Heilig M, Ciccocioppo R (2006) Variation at the rat Crhr1 locus and sensitivity to relapse into alcohol seeking induced by environmental stress. Proc Natl Acad Sci USA 103:15236–15241

    CAS  PubMed  Google Scholar 

  • Harlow HF, Suomi SJ (1974) Induced depression in monkeys. Behav Biol 12:273–296

    CAS  PubMed  Google Scholar 

  • Heilig M, Koob GF (2007) A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci 30(8):399–406

    CAS  PubMed Central  PubMed  Google Scholar 

  • Higley JD, Suomi SJ (1989) Temperamental reactivity in non-human primates. In: Kohnstamm D, Bates HE, Rothbart MK (eds) Temperament in childhood. Wiley, Chichester

    Google Scholar 

  • Higley JD, Hasert MF, Suomi SJ, Linnoila M (1991) Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption. Proc Nat Acad Sci USA 88:7261–7265

    CAS  PubMed  Google Scholar 

  • Higley JD, King ST, Hasert MF, Campoux M, Suomi SJ, Linnoila M (1996a) Stability of interindividual differences in serotonin function and its relationship to severe aggression and competent social behavior in rhesus macaque females. Neuropsychopharmacology 14:67–76

    CAS  Google Scholar 

  • Higley JD, Suomi SJ, Linnoila M (1996b) A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. Alcoholism Clin Exp Res 20:629–642

    CAS  Google Scholar 

  • Hinckers AS, Laucht M, Schmidt MH, Mann KF, Schumann G, Schuckit MA, Heinz A (2006) Low level of response to alcohol as associated with serotonin transporter genotype and high alcohol intake in adolescents. Biol Psychiatry 60(3):282–287

    Google Scholar 

  • Holmes A, Li Q, Murphy DL, Gold E, Crawley JN (2003) Abnormal anxiety-related behavior in serotonin transporter null mutant mice: the influence of genetic background. Genes Brain Behav 26:365–380

    Google Scholar 

  • Hu X, Oroszi G, Chun J, Smith TL, Goldman D, Schuckit MA (2005) An expanded evaluation of the relationship of four alleles to the level of response to alcohol and the alcoholism risk. Alcohol Clin Exp Res 29(1):8–16

    CAS  PubMed  Google Scholar 

  • Hu XZ, Lipsky RH, Zhu G, Akhtar L, Taubman J, Greenberg BD, Xu K, Arnold PD, Richter MA, Kennedy JL, Murphy DL, Goldman D (2006) Additional functional variation at the SLC6A4 gene. Am J Hum Genet 78:815–826

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hundt W, Zimmermann U, Pottig M, Spring K, Holsboer F (2001) The combined dexamethasone-suppression/CRH stimulation test in alcoholics during and after acute withdrawal. Alcohol Clin Exp Res 25:687–691

    CAS  PubMed  Google Scholar 

  • Jaferi A, Bhatnagar S (2007) Corticotropin-releasing hormone receptors in the medial prefrontal cortex regulate HPA activity and anxiety-related behavior regardless of prior stress experience. Brain Res 1186:212–223

    CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson B (2010) Medication treatment of different types of alcoholism. Am J Psychiatry 167:630–639

    PubMed Central  PubMed  Google Scholar 

  • Kagan J, Resnick JS, Snidman N (1988) Biological basis of childhood shyness. Science 240:167–171

    CAS  PubMed  Google Scholar 

  • Kalin NH, Shelton SE (2003) Nonhuman primate models to study anxiety, emotion regulation and psychopathology. Ann NY Acad Sci 1008:189–200

    PubMed  Google Scholar 

  • Kalin NH, Shelton SE, Davidson RJ (2000) Cerebrospinal fluid corticotropin releasing hormone levels are stable in monkeys with patterns of brain activity associated with fearful temperament. Biol Psychiatry 47:579–585

    CAS  PubMed  Google Scholar 

  • Kendler KS, Prescott CA, Myers J, Neale MC (2003) The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Arch Gen Psychiatry 60:929–937

    PubMed  Google Scholar 

  • King BR, Nicholson RC (2007) Advances in understanding corticotrophin-releasing hormone gene expression. Front Biosci 12:581–590

    CAS  PubMed  Google Scholar 

  • Kinnally EL, Capitanio JP, Leibel R, Deng L, Leduc C, Haghighi F, Mann JJ (2010) Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes Brain Behav 9(6):575–582

    Google Scholar 

  • Kinoshita H, Jessop D, Finn DP, Coventry TL, DJ Roberts, Ameno K, Jiri I, Harbuz MS (2001) Acetaldehyde, a metabolite of ethanol, activates the HPA axis in the rat. Alcohol Alcohol 36:59–64

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129

    CAS  PubMed  Google Scholar 

  • Koob GF, Roberts AJ, Kieffer BL, Heyser CJ, Katner SN, Ciccocioppo R, Weiss F (2003) Animal models of motivation for drinking in rodents with a focus on opioid receptor neuropharmacology. Recent Dev Alcohol 16:263–281

    PubMed  Google Scholar 

  • Korte SM, Koolhaas JM, Wingfield JC, McEwen BS (2005) The Darwinian concept of stress: benefits of allostasis and costs of allostatic load and the trade offs in health and disease. Neurosci Biobehav Rev 29:3–38

    PubMed  Google Scholar 

  • Kraemer GW, Moore CF, Newman TK, Barr CS, Schneider ML (2008) Moderate levels of fetal alcohol exposure and serotonin transporter gene promoter polymorphism affect neonatal temperament and LHPA axis regulation in monkeys. Biol Psychiatry 63(3):317–324

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kranzler H, Lappalainen J, Nellissery M, Gelernter J (2002) Association study of alcoholism subtypes with a functional promoter polymorphism in the serotonin transporter protein gene. Alcohol Clin Exp Res 26:1330–1335

    CAS  PubMed  Google Scholar 

  • Krawczak M, Trefilov A, Berard J, Bercovitch F, Kessler M, Sauermann U, Croucher P, Nürnberg P, Widdig A, Schmidtke J (2005) Male reproductive timing in rhesus macaques is influenced by the HTTLPR promoter polymorphism of the serotonin transporter gene. Biol Reprod 72:1109–1113

    CAS  PubMed  Google Scholar 

  • Kreek MJ, LaForge KS, Butelman E (2002) Pharmacotherapy of addictions. Nat Rev Drug Discov; (Review. Erratum in: Nat Rev Drug Discov 2002 Nov;1(11):920. PMID: 12209151) 1(9):710–726

    Google Scholar 

  • Krishnan-Sarin S, Krystal JH, Shi J, Pittman B, O’Malley SS (2007) Family history of alcoholism influences naltrexone-induced reduction in alcohol drinking. Biol Psychiatry 62:694–697

    CAS  PubMed  Google Scholar 

  • Lanfumey L, Mannoury La Cour C, Froger N, Hamon (2000) 5-HT-HPA interactions in two models of transgenic mice relevant to major depression. Neurochem Res 25:1199–1206

    CAS  PubMed  Google Scholar 

  • Lappalainen J, Kranzler HR, Malison R, Price LH, Van Dyck C, Rosenheck RA, Cramer J, Southwick S, Charney D, Krystal J, Gelernter J (2002) A functional neuropeptide Y Leu7Pro polymorphism associated with alcohol dependence in a large population sample from the United States. Arch Gen Psychiatry 59(9):825–831

    CAS  PubMed  Google Scholar 

  • Lesch KP, Meyer J, Glatz K, Flügge G, Hinney A, Hebebrand J, Klauck S, Poustka A, Poustka F, Bengel D, Mössner R, Riederer P, Heils A (1997) The 5-HT transporter gene-linked polymorphic region (5-HTTLPR) in evolutionary perspective: alternative biallelic variation in rhesus monkeys. J Neural Transm 104:1259–1266

    CAS  PubMed  Google Scholar 

  • Li Q, Wichems C, Heils A, Van de Dar LD, Lesch K-P, Murphy DL (1999) Reduction of 5-HT1A binding sites in 5-HT transporter knockout mice J. Pharmacol Exp Ther 291:999–1007

    CAS  Google Scholar 

  • Li Z, Kang SS, Lee S, Rivier C (2005) Effect of ethanol on the regulation of corticotropin releasing factor gene expression. Mol Cell Neurosci 29:345–354

    CAS  PubMed  Google Scholar 

  • Lindell SG, Schwandt ML, Sun H, Sparenborg JD, Bjoerk K, Kasckow JW, Sommer WH, Goldman D, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Functional NPY variation as a factor in stress resilience in rhesus macaques. Arch Gen Psychiatry 67(4):423–431

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lopez JF, Higley JD (2002) The effect of early experience on brain corticosteroid and serotonin receptors in rhesus monkeys. Biol Psychiatry 51:294

    Google Scholar 

  • Lorenz JG, Long JC, Linnoila M, Goldman D, Suomi SJ, Higley JD (2006) Genetic and other contributions to alcohol intake in rhesus macaques (Macaca mulatta). Alcohol Clin Exp Res 30:1–10

    Google Scholar 

  • Lovinger DM, Crabbe JC (2005) Laboratory models of alcoholism: treatment target identification and insight into mechanisms. Nat Neurosci 8(11):1471–1480

    CAS  PubMed  Google Scholar 

  • Luo X, Zuo L, Kranzler H, Zhang H, Wang S, Gelernter J (2008) Multiple OPR genes influence personality traits in substance dependent and healthy subjects in two American populations. Am J Med Genet B Neuropsychiatr Genet 147B:1028–1039

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mazzanti CM, Lappalainen J, Long JC, Bengel D, Naukkarinen H, Eggert M, Virkkunen M, Linnoila M, Goldman D (1998) Role of the serotonin transporter promoter polymorphism in anxiety-related traits. Arch Gen Psychiatry 55:936–940

    CAS  PubMed  Google Scholar 

  • McEwen BS (2006) Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci 8:367–381

    PubMed Central  PubMed  Google Scholar 

  • Mehlman PT, Higley JD, Faucher I, Lilly AA, Taub DM, Vickers J, Suomi SJ, Linnoila M (1994) Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry 151:1485–1491

    CAS  PubMed  Google Scholar 

  • Mehlman PT, Higley JD, Faucher I, Lilly AA, Taub DM, Vickers J, Suomi SJ, Linnoila M (1995) Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates. Am J Psychiatry 152:907–913

    CAS  PubMed  Google Scholar 

  • Meisch RA, Stewart RB (1994) Ethanol as a reinforcer: a revew of laboratory studies of nonhuman primate. Behavioral Pharmacol 5:425–440

    CAS  Google Scholar 

  • Meyer-Lindenberg A, Buckholtz JW, Koachana B, Hariri A, Pezawas L, Blasi G, Wabnitz A, Honea R, Verchinski B, Callicott JH, Egan M, Mattay V, Weinberger DR (2006) Neural mechanisms of genetic risk for impulsivity and violence in humans. Proc Natl Acad Sci USA 103(16):6269–6274

    CAS  PubMed  Google Scholar 

  • Miller GM, Bendor J, Tiefenbacher S, Yang H, Novak MA, Madras BK (2004) A mu-opioid receptor single nucleotide polymorphism in rhesus monkey: association with stress response and aggression. Mol Psychiatry 9(1):99–108

    CAS  PubMed  Google Scholar 

  • Mottagui-Tabar S, Prince JA, Wahlestedt C, Zhu G, Goldman D, Heilig M (2005) A novel single nucleotide polymorphism of the neuropeptide Y (NPY) gene associated with alcohol dependence. Alcohol Clin Exp Res 29(5):702–707

    CAS  PubMed  Google Scholar 

  • Nelson EC, Agrawal A, Pergadia ML, Wang JC, Whitfield HB, Saccone FS, Kern J, Grant JD, Schrage AJ, Rice JP, Montgomery GW, Heath AC, Goate AM, Martin NG, Madden PA (2010) H2 haplotype at chromosome 17q21.31 protects against childhood sexual abuse-associated risk for alcohol consumption and dependence. Addict Biol 15:1–11

    CAS  PubMed Central  PubMed  Google Scholar 

  • Newman TK, Syagailo YV, Barr CS, Wendland JR, Champoux M, Graessle M, Suomi SJ, Higley JD, Lesch KP (2005) Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys. Biol Psychiatry 57:167–172

    CAS  PubMed  Google Scholar 

  • Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR (2004) Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 303:1512–1514

    CAS  PubMed  Google Scholar 

  • Oslin DW, Berrettinini W, Kranzler HR, Pettinati H, Gelernter J, Volpicelli JR, O’Brien CP (2003) A functional polymorphism of the nu-opioid receptor gene is associated with naltrexone response in alcohol-dependent patients. Neuropsychopharmacology 28:146–155

    Google Scholar 

  • Palmour RM, Mulligan J, Howbert JJ, Erivn F (1997) Of monkeys and men: vervets and the genetics of human-like behaviors. Am J Hum Genet 61:481–488

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pang G, Wang J, Wang Z, Goh C, Lee C (2009) The G allele of SNP E1/A118G at the μ-opioid receptor gene locus shows genomic evidence of recent positive selection. Pharmacogenomics 10:1101–1109

    CAS  PubMed  Google Scholar 

  • Parsian A, Cloninger CR (2001) Serotonergic pathway genes and subtypes of alcoholism: association studies. Psychiatr Genet 11:89–94

    CAS  PubMed  Google Scholar 

  • Ramchandani VA, Umhau J, Pavon FJ, Ruiz-Velasco V, Margas W, Sun H, Damadzic R, Eskay R, Schoor M, Thorsell A, Schwandt ML, Sommer WH, George DT, Parsons LH, Herscovitch P, Hommer D, Heilig M (2010) A genetic determinant of striatal dopamine response to alcohol in men. Mol Psychiatry (Epub ahead of print)

    Google Scholar 

  • Ray LA, Hutchison KE (2004) A polymorphism of the mu-opioid receptor gene (OPRM1) and sensitivity to the effects of alcohol in humans. Alcohol Clin Exp Res 28:1789–1795

    CAS  PubMed  Google Scholar 

  • Reich T, Edenberg HJ, Goate A, Williams JT, Rice JP, Van Eerdewegh P, Foroud T, Hesselbrock V, Schuckit MA, Bucholz KK, Porjesz B, Li TK, Conneally PM, Nurnberger JIJ, Tischfield JA, Crowe RR, Cloninger CR, Wu W, Shears S, Carr K, Crose C, Willig C, Begleiter H (1998) Genome-wide search for genes affecting the risk for alcohol dependence. Am J Med Genet 81(3):207–215

    CAS  PubMed  Google Scholar 

  • Sabol SZ, Hu S, Hamer D (1998) A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet 103:273–279

    CAS  PubMed  Google Scholar 

  • Samochowiec J, Lesch KP, Rottmann M, Smolka M, Syagailo YV, Okladnova O, Rommlspacher H, Winterer G, Schmidt LF, Sander T (1999) Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry Res 86:67–72

    CAS  PubMed  Google Scholar 

  • Sanchez MM, Young LJ, Plotsky PM, Insel TR (1999) Autoradiographic and in situ hybridization localization of corticotropin-releasing factor 1 and 2 receptors in nonhuman primate brain. J Comp Neurol 408:365–377

    CAS  PubMed  Google Scholar 

  • Sapolsky RM (2001) Coping with the environment: neural and endocrine mechanisms. In: McEwen BS, Goodman HM (eds): Handbook of Physiology, Oxford University Press, New York

    Google Scholar 

  • Schneider ML, Moore CF, Larson JA, Barr CS, Dejesus OT, Roberts AD (2010) Timing of moderate level prenatal alcohol exposure influences gene expression of sensory processing behavior in rhesus monkeys. Front Integr Neurosci 3:30–38

    Google Scholar 

  • Schuckit MA (1994) Low level of response to alcohol as a predictor of future alcoholism. Am J Psychiatry 15:184–189

    Google Scholar 

  • Schwandt ML, Lindell SG, Sjoberg RL, Chisholm KL, Higley JD, Suomi SJ, Heilig M, Barr CS (2010) Gene-environment interactions and response to social intrusion in male and female rhesus macaques. Biol Psychiatry 67(4):323–330

    PubMed Central  PubMed  Google Scholar 

  • Servatius RJ, Beck KD, Moldow RL, Salameh G, Tumminello TP, Short KR (2005) A stress-induced anxious state in male rats: CRH induces persistent changes in associative learning and startle reactivity. Biol Psychiatry 57:865–872

    CAS  PubMed  Google Scholar 

  • Shannon C, Schwandt ML, Champoux M, Shoaf SE, Suomi SJ, Sinnoila M, Higley JD (2005) Maternal absence and stability of individual differences in CSF 5-HIAA concentrations in rhesus monkey infants. Am J Psychiatry 162:1658–1664

    PubMed  Google Scholar 

  • Shimmin LC, Natarajan S, Ibarguen H, Montasser M, Kim DK, Hanis CL, Boerwinkle E, Wadhwa PD, Hixson JE (2007) Corticotropin releasing hormone (CRH) gene variation: comprehensive resequencing for variant and molecular haplotype discovery in monosomic hybrid cell lines. DNA Seq 18(6):432–442

    Google Scholar 

  • Sinha R, Li CS (2007) Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. Drug Alcohol Rev 26(1):25–31

    PubMed  Google Scholar 

  • Sjoberg RL, Ducci F, Barr CS, Newman TK, Dell’Osso L, Virkkunen M, Goldman D (2008) A non-additive interaction of a functional MAOA VNTR and testosterone predicts antisocial behavior. Neuropsychopharmacology 33(2):425–430

    PubMed Central  PubMed  Google Scholar 

  • Smith MJ, Price GR (1973) The logic of animal conflict. Nature 246:15–18

    Google Scholar 

  • Smoller JW, Rosenbaum JF, Biederman J, Kennedy J, Dai D, Racette SR, Laird NM, Kagan J, Snidman N, Hirshfeld-Becker D, Tsuang MT, Sklar PB, Slaugenhaupt SA (2003) Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition. Biol Psychiatry 54(12):1376–1381

    CAS  PubMed  Google Scholar 

  • Soeby K, Larsen SA, Olsen L, Rasmussen HB, Werge T (2005) Serotonin transporter: evolution and impactof polymorphic transcriptional regulation. Am J Hum Genet 136:53–57

    Google Scholar 

  • Sommer WH, Rimondini R, Hansson AC, Hipskind PA, Gehlert DR, Barr CS, Heilig M (2008) Up-regulation of voluntary alcohol intake, behavioral sensitivity to stress and amygdala Crhr1 expression following a history of dependence. Biol Psychiatry 63(2):139–145

    PubMed  Google Scholar 

  • Sommer WH, Lidström J, Sun H, Passer D, Eskay R, Parker SC, Witt SH, Zimmermann US, Nieratschker V, Rietschel M, Margulies EH, Palkovits M, Laucht M, Heilig M (2010) Human NPY promoter variation rs16147: T > C as a moderator of prefrontal NPY gene expression and negative affect. Hum Mutat 31(8):1594–1608

    Google Scholar 

  • Southwick SM, Vythilingam M, Charney DS (2005) The psychobiology of depression and resilience to stress: implications for prevention and treatment. Annu Rev Clin Psychol 1:255–291

    PubMed  Google Scholar 

  • Spinelli S, Schwandt ML, Lindell SG, Newman TK, Heilig M, Higley JD, Suomi SJ, Goldman D, Barr CS (2007) Association between the rh-5HTTLPR polymorphism and behavior in rhesus macaques during social separation stress. Dev Psychopathol 19(4):977–987

    PubMed  Google Scholar 

  • Spinelli S, Chefer S, Suomi SJ, Higley JD, Barr CS, Stein E (2010a) Early life stress induces long-term morphologic changes in primate brain. Arch Gen Psychiatry 66:658–665

    Google Scholar 

  • Spinelli S, Chefer S, Carson RE, Jagoda E, Lang L, Heilig M, Barr CS, Suomi SJ, Higley JD, Stein E (2010b) Effects of early-life stress on serotonin 1A receptors in juvenile rhesus monkeys measured by PET. Biol Psychiatry (Epub ahead of print)

    Google Scholar 

  • Strome EM, Wheler GH, Higley JD, Loriaux DL, Suomi SJ, Doudet DJ (2002) Intracerebroventricular corticotropin-releasing factor increases limbic glucose metabolism and has social context-dependent behavioral effects in nonhuman primates. Proc Natl Acad Sci USA 99:15749–15754

    CAS  PubMed  Google Scholar 

  • Suomi SJ (1982) Abnormal behavior in nonhuman primates. In: King JE (ed) Primate behavior. Fobes JD. New York, Academinc Press

    Google Scholar 

  • Suomi SJ, Collins ML, Harlow HF, Ruppenthal GC (1976) Effects of maternal and peer separations on young monkeys. J Child Psychol Psychiatry 17:101–112

    CAS  PubMed  Google Scholar 

  • Tabakoff B, Hoffman PL (2000) Animal models in alcohol research. Alcohol Res Health 24:77–84

    CAS  PubMed  Google Scholar 

  • Thorsell A, Repunte-Canonigo V, O’Dell LE, Chen SA, King AR, Lekic D, Koob GF, Sanna PP (2007) Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats. Brain 130:1330–1337

    PubMed Central  PubMed  Google Scholar 

  • Tikkanen R, Sjoberg RL, Ducci F, Goldman D, Holi M, Tiihonen J, Virkkunen (2009) Effects of MAOA-genotype, alcohol consumption and aging on violent behavior. Alcohol Clin Exp Res 33:428–443

    PubMed Central  PubMed  Google Scholar 

  • Trefilov A, Berard J, Krawczak M, Schmidtke J (2000) Natal dispersal in rhesus macaques is related to serotonin transporter gene promoter variation. Behav Genet 30:295–301

    CAS  PubMed  Google Scholar 

  • Vallender EJ, Priddy CM, Hakim S, Yang H, Chen GL, Miller GM (2008) Functional variation in the 3’ UTR of the serotonin transporter in human and rhesus macaque. Genes Brain Behav 7:690–697

    CAS  PubMed  Google Scholar 

  • Vallender EJ, Rüedi-Bettschen D, Miller GM, Platt DM (2010) A pharmacogenetic model of naltrexone-induced attenuation of alcohol consumption in rhesus monkeys. Drug Alcohol Depend 109(1–3):252–256

    Google Scholar 

  • Wagner U, Wahle M, Moritz F, Wagner U, Hantzschel H, Baerwald CG (2006) Promoter polymorphisms regulating corticotrophin-releasing hormone transcription in vitro. Horm Metab Res 38(2):69–75

    CAS  PubMed  Google Scholar 

  • Way BM, Taylor SE, Eisenberger NL (2009) Variation in the μ-opioid receptor gene is associated with dispositional and neural sensitivity to social rejection. Proc Nat Acad Sci USA 106:15079–15084

    CAS  PubMed  Google Scholar 

  • Wendland JR, Lesch KP, Newman TK, Timme A, Gachot-Neveu H, Thierry B, Suomi SJ (2005) differential functional variability of serotonin transporter and monoamine oxidase A genes in Macaque species displaying contrasting levels of aggression-related behavior. Behav Genet 30:1–10

    Google Scholar 

  • Wendland JR, Hampe M, Newman TK, Syagailo Y, Meyer J, Schempp W, Timme A, Suomi SJ, Lesch KP (2006) Structural variation of the monoamine oxidase A gene promoter repeat polymorphism in nonhuman primates. Genes Brain Behav 5:40–45

    CAS  PubMed  Google Scholar 

  • Westergaard GC, Suomi SJ, Chavanne TJ, Houser L, Hurley A, Cleveland A, Snoy PJ, Higley HD (2003) Physiological correlates of aggression and impulsivity in free-ranging female primates. Neuropsychopharmacology 28:1045–1055

    CAS  PubMed  Google Scholar 

  • Williams JB, Spitzer RL, Linzer M, Kroenke K, Hahn SR, deGruy FV, Lazev A (1995) Gender differences in depression in primary care. Am J Obstet Gynecol 173:654–659

    CAS  PubMed  Google Scholar 

  • Williamson DE, Coleman K, Bacanu S, Devlin BJ, Rogers J, Ryan ND, Cameron JL (2003) Heritability of fearful-anxious endophenotypes in infant Rhesus macaques: a preliminary report. Biol Psychiatry 53:284–291

    PubMed  Google Scholar 

  • Wood W, Eagly AH (2002) A cross-cultural analysis of the behavior of women and men: implications for the origins of sex differences. Psychol Bull 128:699–727

    PubMed  Google Scholar 

  • Zhang H, Luo X, Kranzler HR, Lappalainen J, Yang BZ, Krupitsky E, Zvartau E, Gelernter J (2006) Association between two mu-opioid receptor gene (OPRM1) haplotype blocks and drug or alcohol dependence. Hum Mol Genet 15:807–819

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou Z, Zhu G, Hariri AR, Enoch MA, Scott D, Sinha R, Virkkunen M, Mash DC, Lipsky RH, Hu XZ, Hodgkinson CA, Xu K, Buzas B, Yuan Q, Shen PH, Ferrell RE, Manuck SB, Brown SM, Hauger RL, Stohler CS, Zubieta JK, Goldman D (2008) Genetic variation in human NPY expression affects stress response and emotion. Nature 452(7190):997–1001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhu G, Pollak L, Mottagui-Tabar S, Wahlestedt C, Taubman J, Virkkunen M, Goldman D, Heilig M (2003) NPY leu7pro and alcohol dependence in Finnish and Swedish Populations. Alcohol Clin Exp Res 27(1):19–24

    CAS  PubMed  Google Scholar 

  • Zill P, Preuss UW, Koller G, Bondy B, Soyka M (2008) Analysis of single nucleotide polymorphisms and haplotypes in the neuropeptide Y gene: no evidence for association with alcoholism in a German population sample. Alcohol Clin Exp Res 32(3):430–434

    CAS  PubMed  Google Scholar 

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  1. Section of Comparative Behavioral Genomics, NIH/NIAAA/LNG, Rockville, MD, 20852, USA

    Christina S. Barr

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  1. Abt. Psychopharmakologie, Zentralinstitut für Seelische Gesundheit, J 5, Mannheim, 68159, Germany

    Wolfgang H. Sommer

  2. Abt. Psychopharmakologie, Zentralinstitut für Seelische Gesundheit, J 5, Mannheim, 68159, Germany

    Rainer Spanagel

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Barr, C.S. (2011). Non-Human Primate Models of Alcohol-Related Phenotypes: The Influence of Genetic and Environmental Factors. In: Sommer, W., Spanagel, R. (eds) Behavioral Neurobiology of Alcohol Addiction. Current Topics in Behavioral Neurosciences, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-28720-6_142

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