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Sex differences in the effects of adolescent social deprivation on alcohol consumption in μ-opioid receptor knockout mice

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Abstract

Rationale

Evidence based on clinical and experimental animal studies indicates that adolescent social deprivation influences alcohol consumption in a sex-dependent manner, perhaps by influencing stress responses. However, the mechanisms underlying the interaction between these phenomena remain to be elucidated. Since the μ-opioid receptor (MOP) has been reported to have key roles in social stress responses as well as the reinforcing/addictive effects of ethanol, MOP is a candidate molecule that may link adolescent social deprivation and subsequent alterations in alcohol consumption.

Objectives

To evaluate the involvement of MOP and social isolation-induced changes in alcohol consumption, as well as the effect of sex differences on responses to social isolation, alcohol consumption was assessed using a two-bottle home-cage consumption procedure (8 % ethanol vs. water) in MOP knockout (MOP-KO) and wild type (WT) mice of both sexes exposed to adolescent social deprivation or reared socially.

Results

Isolation rearing had no effects upon alcohol consumption of WT mice, whereas it significantly altered alcohol consumption in both male and female MOP-KO mice. Interestingly, social isolation affected ethanol consumption differently in male and female mice. Ethanol consumption was increased in male MOP-KO mice, but decreased in female MOP-KO mice, by isolation rearing.

Conclusion

These results indicate that disturbances of MOP function influence the effects of isolation rearing on ethanol consumption in a sex-dependent manner. Consequently, this suggests the possibility that genetic variation that influences MOP function may have differential roles in alcoholism in men and women, and alcoholism treatments that target MOP function may be differentially effective in males and females.

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References

  • Advani T, Hensler JG, Koek W (2007) Effect of early rearing conditions on alcohol drinking and 5-HT1A receptor function in C57BL/6 J mice. Int J Neuropsychopharmacol 10:595–607

    Article  CAS  PubMed  Google Scholar 

  • Anderson RI, Agoglia AE, Morales M, Varlinskaya EI, Spear LP (2013) Stress, kappa manipulations, and aversive effects of ethanol in adolescent and adult male rats. Neuroscience 249:214–222

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Averna S, Hesselbrock V (2001) The relationship of perceived social support to substance use in offspring of alcoholics. Addict Behav 26:363–374

    Article  CAS  PubMed  Google Scholar 

  • Balldin J, Berglund M, Borg S, Mansson M, Bendtsen P, Franck J, Gustafsson L, Halldin J, Nilsson LH, Stolt G, Willander A (2003) A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence. Alcohol Clin Exp Res 27:1142–1149

    Article  CAS  PubMed  Google Scholar 

  • Brown KJ, Grunberg NE (1995) Effects of housing on male and female rats: crowding stresses male but calm females. Physiol Behav 58:1085–1089

    Article  CAS  PubMed  Google Scholar 

  • Caseras X, Mataix-Cols D, An SK, Lawrence NS, Speckens A, Giampietro V, Brammer MJ, Phillips ML (2007) Sex differences in neural responses to disgusting visual stimuli: implications for disgust-related psychiatric disorders. Biol Psychiatry 62:464–471

    Article  PubMed  Google Scholar 

  • Caviness VS Jr, Kennedy DN, Richelme C, Rademacher J, Filipek PA (1996) The human brain age 7–11 years: a volumetric analysis based on magnetic resonance images. Cereb Cortex 6:726–736

    Article  PubMed  Google Scholar 

  • Chaplin TM, Hong K, Bergquist K, Sinha R (2008) Gender differences in response to emotional stress: an assessment across subjective, behavioral, and physiological domains and relations to alcohol craving. Alcohol Clin Exp Res 32:1242–1250

    Article  PubMed Central  PubMed  Google Scholar 

  • Chester JA, de Paula Barrenha G, DeMaria A, Finegan A (2006) Different effects of stress on alcohol drinking behaviour in male and female mice selectively bred for high alcohol preference. Alcohol Alcohol 41:44–53

    Article  PubMed  Google Scholar 

  • Cosgrove KP, Mazure CM, Staley JK (2007) Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry 62:847–855

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cruz FC, Quadros IM, Planeta Cda S, Miczek KA (2008) Maternal separation stress in male mice: long-term increases in alcohol intake. Psychopharmacol (Berl) 201:459–468

    Article  CAS  Google Scholar 

  • Dahan A, Kest B, Waxman AR, Sarton E (2008) Sex-specific responses to opiates: animal and human studies. Anesth Analg 107:83–95

    Article  CAS  PubMed  Google Scholar 

  • Dawson DA, Grant BF, Ruan WJ (2005) The association between stress and drinking: modifying effects of gender and vulnerability. Alcohol Alcohol 40:453–460

    Article  PubMed  Google Scholar 

  • Diaz SL, Barros VG, Antonelli MC, Rubio MC, Balerio GN (2006) Morphine withdrawal syndrome and its prevention with baclofen: autoradiographic study of mu-opioid receptors in prepubertal male and female mice. Synapse 60:132–140

    Article  CAS  PubMed  Google Scholar 

  • Dufouil C, Ducimetiere P, Alperovitch A (1997) Sex differences in the association between alcohol consumption and cognitive performance. EVA study group. epidemiology of vascular aging. Am J Epidemiol 146:405–412

    Article  CAS  PubMed  Google Scholar 

  • Enoch MA (2012) The influence of gene-environment interactions on the development of alcoholism and drug dependence. Curr Psychiat Rep 14:150–158

    Article  Google Scholar 

  • Fuchs PN, Roza C, Sora I, Uhl G, Raja SN (1999) Characterization of mechanical withdrawal responses and effects of mu-, delta- and kappa-opioid agonists in normal and mu-opioid receptor knockout mice. Brain Res 821:480–486

    Article  CAS  PubMed  Google Scholar 

  • Gentsch C, Lichtsteiner M, Kraeuchi K, Feer H (1982) Different reaction patterns in individually and socially reared rats during exposures to novel environments. Behav Brain Res 4:45–54

    Article  CAS  PubMed  Google Scholar 

  • Gianoulakis C (2001) Influence of the endogenous opioid system on high alcohol consumption and genetic predisposition to alcoholism. J Psychiatry Neurosci 26:304–318

    PubMed Central  CAS  PubMed  Google Scholar 

  • Giedd JN, Vaituzis AC, Hamburger SD, Lange N, Rajapakse JC, Kaysen D, Vauss YC, Rapoport JL (1996) Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: ages 4–18 years. J Comp Neurol 366:223–230

    Article  CAS  PubMed  Google Scholar 

  • Goldstein JM, Jerram M, Abbs B, Whitfield-Gabrieli S, Makris N (2010) Sex differences in stress response circuitry activation dependent on female hormonal cycle. J Neurosci 30:431–438

    Article  PubMed Central  PubMed  Google Scholar 

  • Hall FS (1998) Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences. Crit Rev Neurobiol 12:129–162

    Article  CAS  PubMed  Google Scholar 

  • Hall FS, Perona MT (2012) Have studies of the developmental regulation of behavioral phenotypes revealed the mechanisms of gene-environment interactions? Physiol Behav 107:623–640

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hall FS, Perona MTG (2013) The role of serotonin in the neurodevelopmental consequences of early social experience. In: Hall FS (ed) Serotonin: biosynthesis, regulation and health implications. Nova, New York, pp 168–187

    Google Scholar 

  • Hall FS, Uhl GR (2006) Transgenic mouse studies reveal substantial roles for opioid receptors in the rewarding effects of several classes of addictive drug. Curr Psychiatr Rev 2:27–37

    Article  CAS  Google Scholar 

  • Hall FS, Huang S, Fong GF, Pert A (1998a) The effects of social isolation on the forced swim test in Fawn Hooded and Wistar rats. J Neurosci Methods 79:47–51

    Article  CAS  PubMed  Google Scholar 

  • Hall FS, Huang S, Fong GW, Pert A, Linnoila M (1998b) Effects of isolation-rearing on locomotion, anxiety and responses to ethanol in Fawn Hooded and Wistar rats. Psychopharmacol(Berl) 139:203–209

    Article  CAS  Google Scholar 

  • Hall FS, Huang S, Fong GW, Pert A, Linnoila M (1998c) Effects of isolation-rearing on voluntary consumption of ethanol, sucrose and saccharin solutions in Fawn Hooded and Wistar rats. Psychopharmacol (Berl) 139:210–216

    Article  CAS  Google Scholar 

  • Hall FS, Wilkinson LS, Humby T, Inglis W, Kendall DA, Marsden CA, Robbins TW (1998d) Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems. Pharmacol Biochem Behav 59:859–872

    Article  CAS  PubMed  Google Scholar 

  • Hall FS, Sora I, Uhl GR (2001) Ethanol consumption and reward are decreased in mu-opiate receptor knockout mice. Psychopharmacol (Berl) 154:43–49

    Article  CAS  Google Scholar 

  • Hall FS, Golub SO, Houston-Ludlam AN (2013) Issues in the study of alcohol consumption in genetically modified mice. Journal of Alcoholism and Drug Dependence 1

  • Haller J, Fuchs E, Halasz J, Makara GB (1999) Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats. Brain Res Bull 50:33–39

    Article  CAS  PubMed  Google Scholar 

  • Hardie TL, Moss HB, Lynch KG (2008) Sex differences in the heritability of alcohol problems. Am J Addict 17:319–327

    Article  PubMed  Google Scholar 

  • He DY, McGough NN, Ravindranathan A, Jeanblanc J, Logrip ML, Phamluong K, Janak PH, Ron D (2005) Glial cell line-derived neurotrophic factor mediates the desirable actions of the anti-addiction drug ibogaine against alcohol consumption. J Neurosci 25:619–628

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • He SQ, Zhang ZN, Guan JS, Liu HR, Zhao B, Wang HB, Li Q, Yang H, Luo J, Li ZY, Wang Q, Lu YJ, Bao L, Zhang X (2011) Facilitation of μ-opioid receptor activity by preventing δ-opioid receptor-mediated codegradation. Neuron 69:120–131

    Article  CAS  PubMed  Google Scholar 

  • Heinrichs SC, Koob GF (2006) Application of experimental stressors in laboratory rodents. Curr Protoc Neurosci Chapter 8: Unit8 4

  • Herz A (1997) Endogenous opioid systems and alcohol addiction. Psychopharmacol (Berl) 129:99–111

    Article  CAS  Google Scholar 

  • Hong S, Flashner B, Chiu M, ver Hoeve E, Luz S, Bhatnagar S (2012) Social isolation in adolescence alters behaviors in the forced swim and sucrose preference tests in female but not in male rats. Physiol Behav 105:269–275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Iwamoto ET (1985) Place-conditioning properties of mu, kappa, and sigma opioid agonists. Alcohol Drug Res 6:327–339

    CAS  PubMed  Google Scholar 

  • Jarjour S, Bai L, Gianoulakis C (2009) Effect of acute ethanol administration on the release of opioid peptides from the midbrain including the ventral tegmental area. Alcohol Clin Exp Res 33:1033–1043

    Article  CAS  PubMed  Google Scholar 

  • Jernigan DH, Ostroff J, Ross C, O’Hara JA 3rd (2004) Sex differences in adolescent exposure to alcohol advertising in magazines. Arch Pediatr Adolesc Med 158:629–634

    Article  PubMed  Google Scholar 

  • Job MO, Tang A, Hall FS, Sora I, Uhl GR, Bergeson SE, Gonzales RA (2007) Mu (mu) opioid receptor regulation of ethanol-induced dopamine response in the ventral striatum: evidence of genotype specific sexual dimorphic epistasis. Biol Psychiatry 62:627–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kendler KS, Sheth K, Gardner CO, Prescott CA (2002) Childhood parental loss and risk for first-onset of major depression and alcohol dependence: the time-decay of risk and sex differences. Psychol Med 32:1187–1194

    CAS  PubMed  Google Scholar 

  • Komatsu H, Ohara A, Sasaki K, Abe H, Hattori H, Hall FS, Uhl GR, Sora I (2011) Decreased response to social defeat stress in μ-opioid-receptor knockout mice. Pharmacol Biochem Behav 99:676–682

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kovacs KM, Szakall I, O’Brien D, Wang R, Vinod KY, Saito M, Simonin F, Kieffer BL, Vadasz C (2005) Decreased oral self-administration of alcohol in kappa-opioid receptor knock-out mice. Alcohol Clin Exp Res 29:730–738

    Article  CAS  PubMed  Google Scholar 

  • Kozlov AP, Nizhnikov ME, Kramskaya TA, Varlinskaya EI, Spear NE (2013) mu-Opioid blockade reduces ethanol effects on intake and behavior of the infant rat during short-term but not long-term social isolation. Pharmacol Biochem Behav 103:773–782

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Kreek MJ, Koob GF (1998) Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend 51:23–47

    Article  CAS  PubMed  Google Scholar 

  • Lodge DJ, Lawrence AJ (2003) The effect of isolation rearing on volitional ethanol consumption and central CCK/dopamine systems in Fawn-Hooded rats. Behav Brain Res 141:113–122

    Article  CAS  PubMed  Google Scholar 

  • Longoni R, Cadoni C, Mulas A, Di Chiara G, Spina L (1998) Dopamine-dependent behavioural stimulation by non-peptide delta opioids BW373U86 and SNC 80: 2. Place-preference and brain microdialysis studies in rats. Behav Pharmacol 9:9–14

    CAS  PubMed  Google Scholar 

  • Lopez MF, Doremus-Fitzwater TL, Becker HC (2011) Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6 J mice. Alcohol 45:355–364

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Marinelli PW, Quirion R, Gianoulakis C (2003) A microdialysis profile of beta-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration. Psychopharmacol (Berl) 169:60–67

    Article  CAS  Google Scholar 

  • Matsuda T, Sakaue M, Ago Y, Sakamoto Y, Koyama Y, Baba A (2001) Functional alteration of brain dopaminergic system in isolated aggressive mice. Nihon Shinkei Seishin Yakurigaku Zasshi 21:71–76

    CAS  PubMed  Google Scholar 

  • McCall NM, Sprow GM, Delpire E, Thiele TE, Kash TL, Pleil KE (2013) Effects of sex and deletion of neuropeptide Y2 receptors from GABAergic neurons on affective and alcohol drinking behaviors in mice. Front Integr Neurosci 7:100

    Article  PubMed Central  PubMed  Google Scholar 

  • McCool BA, Chappell AM (2009) Early social isolation in male long-Evans rats alters both appetitive and consummatory behaviors expressed during operant ethanol self-administration. Alcohol Clin Exp Res 33:273–282

    Article  PubMed Central  PubMed  Google Scholar 

  • Melón LC, Wray KN, Moore EM, Boehm SL 2nd (2013) Sex and age differences in heavy binge drinking and its effects on alcohol responsivity following abstinence. Pharmacol Biochem Behav 104:177–187

    Article  PubMed Central  PubMed  Google Scholar 

  • Milner TA, Burstein SR, Marrone GF, Khalid S, Gonzalez AD, Williams TJ, Schierberl KC, Torres-Reveron A, Gonzales KL, McEwen BS, Waters EM (2013) Stress differentially alters mu opioid receptor density and trafficking in parvalbumin-containing interneurons in the female and male rat hippocampus. Synapse 67:757–772

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morris PL, Hopwood M, Whelan G, Gardiner J, Drummond E (2001) Naltrexone for alcohol dependence: a randomized controlled trial. Addiction 96:1565–1573

    Article  CAS  PubMed  Google Scholar 

  • Olive MF, Koenig HN, Nannini MA, Hodge CW (2001) Stimulation of endorphin neurotransmission in the nucleus accumbens by ethanol, cocaine, and amphetamine. J Neurosci 21:RC184

    CAS  PubMed  Google Scholar 

  • O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B (1992) Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 49:881–887

    Article  PubMed  Google Scholar 

  • Palanza P, Gioiosa L, Parmigiani S (2001) Social stress in mice: gender differences and effects of estrous cycle and social dominance. Physiol Behav 73:411–420

    Article  CAS  PubMed  Google Scholar 

  • Pietropaolo S, Singer P, Feldon J, Yee BK (2008) The postweaning social isolation in C57BL/6 mice: preferential vulnerability in the male sex. Psychopharmacol (Berl) 197:613–628

    Article  CAS  Google Scholar 

  • Prescott CA, Kendler KS (1999) Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatry 156:34–40

    Article  CAS  PubMed  Google Scholar 

  • Prescott CA, Aggen SH, Kendler KS (1999) Sex differences in the sources of genetic liability to alcohol abuse and dependence in a population-based sample of U.S. twins. Alcohol Clin Exp Res 23:1136–1144

    Article  CAS  PubMed  Google Scholar 

  • Pryce CR, Ruedi-Bettschen D, Dettling AC, Weston A, Russig H, Ferger B, Feldon J (2005) Long-term effects of early-life environmental manipulations in rodents and primates: potential animal models in depression research. Neurosci Biobehav Rev 29:649–674

    Article  PubMed  Google Scholar 

  • Ramachandra V, Kang F, Kim C, Nova AS, Bajaj A, Hall FS, Uhl GR, Gonzales RA (2011) The MU opioid receptor is not involved in ethanol-stimulated dopamine release in the ventral striatum of C57BL/6 J Mice. Alcohol Clin Exp Res 35:929–938

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Roberts AJ, McDonald JS, Heyser CJ, Kieffer BL, Matthes HW, Koob GF, Gold LH (2000) mu-Opioid receptor knockout mice do not self-administer alcohol. J Pharmacol Exp Ther 293:1002–1008

    CAS  PubMed  Google Scholar 

  • Roberts AJ, Gold LH, Polis I, McDonald JS, Filliol D, Kieffer BL, Koob GF (2001) Increased ethanol self-administration in delta-opioid receptor knockout mice. Alcohol Clin Exp Res 25:1249–1256

    CAS  PubMed  Google Scholar 

  • Rodefer JS, Campbell UC, Cosgrove KP, Carroll ME (1999) Naltrexone pretreatment decreases the reinforcing effectiveness of ethanol and saccharin but not PCP or food under concurrent progressive-ratio schedules in rhesus monkeys. Psychopharmacol (Berl) 141:436–446

    Article  CAS  Google Scholar 

  • Sasaki K, Sumiyoshi A, Nonaka H, Kasahara Y, Ikeda K, Hall FS, Uhl GR, Watanabe M, Kawashima R, Sora I (2014) Specific regions display altered gray matter volume in mu-opioid receptor knockout (MOP-KO) mice: MRI voxel - based morphometry. Br J Pharmacol

  • Schenk S, Gorman K, Amit Z (1990) Age-dependent effects of isolation housing on the self-administration of ethanol in laboratory rats. Alcohol 7:321–326

    Article  CAS  PubMed  Google Scholar 

  • Schienle A, Schafer A, Stark R, Walter B, Vaitl D (2005) Gender differences in the processing of disgust- and fear-inducing pictures: an fMRI study. Neuroreport 16:277–280

    Article  PubMed  Google Scholar 

  • Sisk CL, Zehr JL (2005) Pubertal hormones organize the adolescent brain and behavior. Front Neuroendocrinol 26:163–174

    Article  CAS  PubMed  Google Scholar 

  • Siviy SM, Panksepp J (2011) In search of the neurobiological substrates for social playfulness in mammalian brains. Neurosci Biobehav Rev 35:1821–1830

    Article  PubMed  Google Scholar 

  • Sora I, Funada M, Uhl GR (1997a) The mu-opioid receptor is necessary for [D-Pen2, D-Pen5]enkephalin-induced analgesia. Eur J Pharmacol 324:R1–R2

    Article  CAS  PubMed  Google Scholar 

  • Sora I, Takahashi N, Funada M, Ujike H, Revay RS, Donovan DM, Miner LL, Uhl GR (1997b) Opiate receptor knockout mice define mu receptor roles in endogenous nociceptive responses and morphine-induced analgesia. Proc Natl Acad Sci U S A 94:1544–1549

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Soyka M (2013) Review: In alcohol use disorders, acamprosate is more effective for inducing abstinence while naltrexone is more effective for reducing heavy drinking and craving. Evid Based Ment Health 16:71

    Article  PubMed  Google Scholar 

  • Terenius L (1996) Alcohol addiction (alcoholism) and the opioid system. Alcohol 13:31–34

    Article  CAS  PubMed  Google Scholar 

  • Thorsell A, Slawecki CJ, Khoury A, Mathe AA, Ehlers CL (2005) Effect of social isolation on ethanol consumption and substance P/neurokinin expression in Wistar rats. Alcohol 36:91–97

    Article  CAS  PubMed  Google Scholar 

  • Trezza V, Campolongo P, Vanderschuren LJ (2011) Evaluating the rewarding nature of social interactions in laboratory animals. Dev Cogn Neurosci 1:444–458

    Article  PubMed  Google Scholar 

  • Trigo JM, Martin-Garcia E, Berrendero F, Robledo P, Maldonado R (2010) The endogenous opioid system: a common substrate in drug addiction. Drug Alcohol Depend 108:183–194

    Article  CAS  PubMed  Google Scholar 

  • Uhart M, Wand GS (2009) Stress, alcohol and drug interaction: an update of human research. Addict Biol 14:43–64

    Article  PubMed Central  CAS  PubMed  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 

  • Vanderschuren LJ, Niesink RJ, Spruijt BM, Van Ree JM (1995) Mu- and kappa-opioid receptor-mediated opioid effects on social play in juvenile rats. Eur J Pharmacol 276:257–266

    Article  CAS  PubMed  Google Scholar 

  • Varlinskaya EI, Spear LP (2009) Ethanol-induced social facilitation in adolescent rats: role of endogenous activity at mu opioid receptors. Alcohol Clin Exp Res 33:991–1000

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP (1992) Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry 49:876–880

    Article  CAS  PubMed  Google Scholar 

  • Wee S, Koob GF (2010) The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse. Psychopharmacol (Berl) 210:121–135

    Article  CAS  Google Scholar 

  • Wei J, Yuen EY, Liu W, Li X, Zhong P, Karatsoreos IN, McEwen BS, Yan Z (2014) Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Mol Psychiatry 19:588–598

    Article  CAS  PubMed  Google Scholar 

  • Wilkinson LS, Killcross SS, Humby T, Hall FS, Geyer MA, Robbins TW (1994) Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition. Neuropsychopharmacology 10:61–72

    Article  CAS  PubMed  Google Scholar 

  • Wolffgramm J (1990) Free choice ethanol intake of laboratory rats under different social conditions. Psychopharmacol (Berl) 101:233–239

    Article  CAS  Google Scholar 

  • Zubieta JK, Dannals RF, Frost JJ (1999) Gender and age influences on human brain mu-opioid receptor binding measured by PET. Am J Psychiatry 156:842–848

    Article  CAS  PubMed  Google Scholar 

  • Zubieta JK, Smith YR, Bueller JA, Xu Y, Kilbourn MR, Jewett DM, Meyer CR, Koeppe RA, Stohler CS (2002) mu-opioid receptor-mediated antinociceptive responses differ in men and women. J Neurosci 22:5100–5107

    CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a Japan Society for the Promotion Science (JSPS) KAKENHI Grant-in-Aid for JSPS Fellows (254961); by an Intramural Research Grant for Collaboration on Special Project Research from IRIDeS, Tohoku University, JSPS Grant-in-Aid for scientific research on innovative areas (24116007); by a Grant-in-Aid for Health and Labour Science Research (Research on Pharmaceutical and Medical Safety) from MHLW of Japan; by a Grant from the Ministry of Health, Labour and Welfare of Japan; by the Global COE Program (Basic & Translational Research Center for Global Brain Science) from MEXT of Japan; and through funding from the Intramural Research Program of the National Institute on Drug Abuse, NIH/DHHS, USA (GRU and FSH).

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  1. F. Scott Hall

    Present address: Department of Pharmacology, University of Toledo College of Pharmacy and Pharmaceutical Sciences, Toledo, OH, USA

Authors and Affiliations

  1. Department of Biological Psychiatry, Tohoku University, Sendai, Japan

    Yuki Moriya, Yoshiyuki Kasahara, Yasufumi Sakakibara, Hiroaki Tomita & Ichiro Sora

  2. Department of Disaster Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan

    Yuki Moriya, Yoshiyuki Kasahara, Yasufumi Sakakibara & Hiroaki Tomita

  3. International Research Institute of Disaster Science (IRIDeS), Tohoku University, Sendai, Japan

    Yuki Moriya, Yoshiyuki Kasahara, Yasufumi Sakakibara & Hiroaki Tomita

  4. Tohoku Medical Megabank Organization (ToMMo), Tohoku University, Sendai, Japan

    Hiroaki Tomita

  5. Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Bethesda, MD, 20892, USA

    F. Scott Hall & George R. Uhl

  6. Department of Psychiatry, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 657-0017, Japan

    Ichiro Sora

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Moriya, Y., Kasahara, Y., Hall, F.S. et al. Sex differences in the effects of adolescent social deprivation on alcohol consumption in μ-opioid receptor knockout mice. Psychopharmacology 232, 1471–1482 (2015). https://doi.org/10.1007/s00213-014-3784-y

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