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Vasopressin and alcohol: a multifaceted relationship

Psychopharmacology volume 235, pages 3363–3379 (2018)Cite this article

Abstract

Background

Arginine vasopressin (VP) has been implicated in a number of neuropsychiatric disorders with an emphasis on situations where stress increased the severity of the disorder. Based on this hypothesized role for VP in neuropsychiatric disorders, much research is currently being undertaken in humans and animals to test VP as a target for treatment of a number of these disorders including alcohol abuse.

Objectives

To provide a summary of the literature regarding the role of VP in alcohol- and stress-related behaviors including the use of drugs that target VP in clinical trials.

Results

Changes in various components of the VP system occur with alcohol and stress. Manipulating VP or its receptors can alter alcohol- and stress-related behaviors including tolerance to alcohol, alcohol drinking, and anxiety-like behavior. Finally, the hypothalamic–pituitary–adrenal axis response to alcohol is also altered by manipulating the VP system. However, clinical trials of VP antagonists have had mixed results.

Conclusions

A review of VP’s involvement in alcohol’s actions demonstrates that there is much to be learned about brain regions involved in VP-mediated effects on behavior. Thus, future work should focus on elucidating relevant brain regions. By using previous knowledge of the actions of VP and determining the brain regions and/or systems involved in its different behavioral effects, it may be possible to identify a specific receptor subtype target, drug treatment combination, or specific clinical contexts that may point toward a more successful treatment.

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Fig. 1

Abbreviations

AA:

alcohol-preferring

ACTH:

adrenocorticotropic hormone

AMY:

amygdala

ANA:

alcohol non-preferring

AUD:

alcohol use disorder

BST:

bed nucleus of the stria terminalis

cAMP:

cyclic adenosine 3′,5′-monophosphate

CeA:

central nucleus of the amygdala

CORT:

corticosterone

CRF:

corticotropin- releasing factor

CRF-R1:

corticotropin-releasing factor receptor 1

CRF-R2:

corticotropin-releasing factor receptor 2

DGAVP:

des-Gly9-[Arg8]-vasopressin dicitrate

DMH:

dorsomedial hypothalamic nucleus

DR:

dorsal raphe

DSM-5:

Diagnostic and Statistical Manual of Mental Disorders, 5th Edition

GABA:

gamma-aminobutyric acid

HAD:

high alcohol-drinking

HPA:

hypothalamic–pituitary–adrenal

HPC:

hippocampus

LBH:

lateral habenular nucleus

LC:

locus coeruleus

LS:

lateral septum

MeA:

medial amygdala

MPO AH:

medial preoptic area–anterior hypothalamus

mRNA:

messanger RNA

OT:

oxytocin

*OT:

olfactory tubercle

P:

alcohol-preferring

PAG:

periaqueductal gray

PIP2:

phosphatidylinositol 4,5-bisphosphate

POMS:

profile of mood states

PV:

periventricular nucleus hypothalamus

PVN:

paraventricular nucleus

SCN:

suprachiasmatic nucleus

SON:

supraoptic nucleus

STAI:

Spielberger trait anxiety index

V1a:

vasopressin 1a receptor

V1b:

vasopressin 1b receptor

V2:

vasopressin 2 receptor

VOLT:

vascular organ of the lamina terminalis

VP:

arginine vasopressin

*VP:

ventral pallidum

References

  • Aguilera G, Rabadan-Diehl C (2000) Vasopressinergic regulation of the hypothalamic-pituitary-adrenal axis: implications for stress adaptation. Regul Pept 96:23–29

    CAS  PubMed  Google Scholar 

  • APA (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Association

  • Appenrodt E, Schnabel R, Schwarzberg H (1998) Vasopressin administration modulates anxiety-related behavior in rats. Physiol Behav 64:543–547

    CAS  PubMed  Google Scholar 

  • Barberis C, Tribollet E (1996) Vasopressin and oxytocin receptors in the central nervous system. Crit Rev Neurobiol 10:119–154

    CAS  PubMed  Google Scholar 

  • Bartanusz V, Aubry JM, Jezova D, Baffi J, Kiss JZ (1993) Up-regulation of vasopressin mRNA in paraventricular hypophysiotrophic neurons after acute immobilization stress. Neuroendocrinology 58:625–629

    CAS  PubMed  Google Scholar 

  • Bielsky IF, Hu SB, Szegda KL, Westphal H, Young LJ (2004) Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29:483–493

    CAS  PubMed  Google Scholar 

  • Bielsky IF, Hu SB, Young LJ (2005) Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice. Behav Brain Res 164:132–136

    CAS  PubMed  Google Scholar 

  • Bleickardt CJ, Mullins DE, Macsweeney CP, Werner BJ, Pond AJ, Guzzi MF, Martin FD, Varty GB, Hodgson RA (2009) Characterization of the V1a antagonist, JNJ-17308616, in rodent models of anxiety-like behavior. Psychopharmacology 202:711–718

    CAS  PubMed  Google Scholar 

  • Breese GR, Knapp DJ (2016) Persistent adaptation by chronic alcohol is facilitated by neuroimmune activation linked to stress and CRF. Alcohol 52:9–23

    CAS  PubMed  PubMed Central  Google Scholar 

  • Breese GR, Chu K, Dayas CV, Funk D, Knapp DJ, Koob GF, Le DA, O’Dell LE, Overstreet DH, Roberts AJ, Sinha R, Valdez GR, Weiss F (2005a) Stress enhancement of craving during sobriety: a risk for relapse. Alcohol Clin Exp Res 29:185–195

    PubMed  PubMed Central  Google Scholar 

  • Breese GR, Overstreet DH, Knapp DJ, Navarro M (2005b) Prior multiple ethanol withdrawals enhance stress-induced anxiety-like behavior: inhibition by CRF1- and benzodiazepine-receptor antagonists and a 5-HT1a-receptor agonist. Neuropsychopharmacology 30:1662–1669

    CAS  PubMed  PubMed Central  Google Scholar 

  • Breese GR, Sinha R, Heilig M (2011) Chronic alcohol neuroadaptation and stress contribute to susceptibility for alcohol craving and relapse. Pharmacol Ther 129:149–171

    CAS  PubMed  Google Scholar 

  • Buijs RM (1978) Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat. Pathways to the limbic system, medulla oblongata and spinal cord. Cell Tissue Res 192:423–435

    CAS  PubMed  Google Scholar 

  • Buijs RM (1980) Immunocytochemical demonstration of vasopressin and oxytocin in the rat brain by light and electron microscopy. J Histochem Cytochem 28:357–360

    CAS  PubMed  Google Scholar 

  • Bunck M, Czibere L, Horvath C, Graf C, Frank E, Kessler MS, Murgatroyd C, Muller-Myhsok B, Gonik M, Weber P, Putz B, Muigg P, Panhuysen M, Singewald N, Bettecken T, Deussing JM, Holsboer F, Spengler D, Landgraf R (2009) A hypomorphic vasopressin allele prevents anxiety-related behavior. PLoS One 4:e5129

    PubMed  PubMed Central  Google Scholar 

  • Caffe AR, van Leeuwen FW, Luiten PG (1987) Vasopressin cells in the medial amygdala of the rat project to the lateral septum and ventral hippocampus. J Comp Neurol 261:237–252

    CAS  PubMed  Google Scholar 

  • Caldwell HK, Stewart J, Wiedholz LM, Millstein RA, Iacangelo A, Holmes A, Young WS 3rd, Wersinger SR (2006) The acute intoxicating effects of ethanol are not dependent on the vasopressin 1a or 1b receptors. Neuropeptides 40:325–337

    CAS  PubMed  Google Scholar 

  • Carmona-Calero E, del Mar Perez-Delgado M, Banuelos-Pineda J, Marrero-Gordillo N, Ferres-Torres R, Castaneyra-Perdomo A (1995) Effects of chronic alcohol intake on the vasopressin content in the hypothalamic paraventricular and supraoptic nuclei of the mouse. An immunohistochemical and morphometric study. Drug Alcohol Depend 38:19–24

    CAS  PubMed  Google Scholar 

  • Carter CS (2007) Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders? Behav Brain Res 176:170–186

    CAS  PubMed  Google Scholar 

  • Chen C, Diaz Brinton RD, Shors TJ, Thompson RF (1993) Vasopressin induction of long-lasting potentiation of synaptic transmission in the dentate gyrus. Hippocampus 3:193–203

    CAS  PubMed  Google Scholar 

  • Chen X, Hackett PD, DeMarco AC, Feng C, Stair S, Haroon E, Ditzen B, Pagnoni G, Rilling JK (2016) Effects of oxytocin and vasopressin on the neural response to unreciprocated cooperation within brain regions involved in stress and anxiety in men and women. Brain Imaging Behav 10:581–593

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chepkova AN, Kapai NA, Skrebitskii VG (2001) Arginine vasopressin fragment AVP(4-9) facilitates induction of long-term potentiation in the hippocampus. Bull Exp Biol Med 131:136–138

    CAS  PubMed  Google Scholar 

  • Collins GB, Brosnihan KB, Zuti RA, Messina M, Gupta MK (1992) Neuroendocrine, fluid balance, and thirst responses to alcohol in alcoholics. Alcohol Clin Exp Res 16:228–233

    CAS  PubMed  Google Scholar 

  • Crews FT, Vetreno RP, Broadwater MA, Robinson DL (2016) Adolescent alcohol exposure persistently impacts adult neurobiology and behavior. Pharmacol Rev 68:1074–1109

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dannenhoffer CA, Kim EU, Saalfield J, Werner DF, Varlinskaya EI, Spear LP (2018) Oxytocin and vasopressin modulation of social anxiety following adolescent intermittent ethanol exposure. Psychopharmacology 235:3065–3077

    CAS  PubMed  Google Scholar 

  • de Goeij DC, Jezova D, Tilders FJ (1992) Repeated stress enhances vasopressin synthesis in corticotropin releasing factor neurons in the paraventricular nucleus. Brain Res 577:165–168

    PubMed  Google Scholar 

  • de Guglielmo G, Crawford E, Kim S, Vendruscolo LF, Hope BT, Brennan M, Cole M, Koob GF, George O (2016) Recruitment of a neuronal ensemble in the central nucleus of the amygdala is required for alcohol dependence. J Neurosci 36:9446–9453

    PubMed  PubMed Central  Google Scholar 

  • De Vries GJ, Buijs RM (1983) The origin of the vasopressinergic and oxytocinergic innervation of the rat brain with special reference to the lateral septum. Brain Res 273:307–317

    PubMed  Google Scholar 

  • De Vries GJ, Panzica GC (2006) Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints. Neuroscience 138:947–955

    PubMed  Google Scholar 

  • DeVries GJ, Buijs RM, Van Leeuwen FW, Caffe AR, Swaab DF (1985) The vasopressinergic innervation of the brain in normal and castrated rats. J Comp Neurol 233:236–254

    CAS  PubMed  Google Scholar 

  • DiBenedictis BT, Nussbaum ER, Cheung HK, Veenema AH (2017) Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network. J Comp Neurol 525:2549–2570

    CAS  PubMed  PubMed Central  Google Scholar 

  • Doring WK, Herzenstiel MN, Krampe H, Jahn H, Pralle L, Sieg S, Wegerle E, Poser W, Ehrenreich H (2003) Persistent alterations of vasopressin and N-terminal proatrial natriuretic peptide plasma levels in long-term abstinent alcoholics. Alcohol Clin Exp Res 27:849–861

    PubMed  Google Scholar 

  • Dumais KM, Veenema AH (2016) Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior. Front Neuroendocrinol 40:1–23

    CAS  PubMed  Google Scholar 

  • Duque-Wilckens N, Steinman MQ, Laredo SA, Hao R, Perkeybile AM, Bales KL, Trainor BC (2016) Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects. Neuropharmacology 110:59–68

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ebner K, Wotjak CT, Holsboer F, Landgraf R, Engelmann M (1999) Vasopressin released within the septal brain area during swim stress modulates the behavioural stress response in rats. Eur J Neurosci 11:997–1002

    CAS  PubMed  Google Scholar 

  • Ebner K, Wotjak CT, Landgraf R, Engelmann M (2002) Forced swimming triggers vasopressin release within the amygdala to modulate stress-coping strategies in rats. Eur J Neurosci 15:384–388

    PubMed  Google Scholar 

  • Edwards S, Guerrero M, Ghoneim OM, Roberts E, Koob GF (2012) Evidence that vasopressin V1b receptors mediate the transition to excessive drinking in ethanol-dependent rats. Addict Biol 17:76–85

    CAS  PubMed  Google Scholar 

  • Egashira N, Tanoue A, Higashihara F, Fuchigami H, Sano K, Mishima K, Fukue Y, Nagai H, Takano Y, Tsujimoto G, Stemmelin J, Griebel G, Iwasaki K, Ikeda T, Nishimura R, Fujiwara M (2005) Disruption of the prepulse inhibition of the startle reflex in vasopressin V1b receptor knockout mice: reversal by antipsychotic drugs. Neuropsychopharmacology 30:1996–2005

    CAS  PubMed  Google Scholar 

  • Egashira N, Tanoue A, Matsuda T, Koushi E, Harada S, Takano Y, Tsujimoto G, Mishima K, Iwasaki K, Fujiwara M (2007) Impaired social interaction and reduced anxiety-related behavior in vasopressin V1a receptor knockout mice. Behav Brain Res 178:123–127

    CAS  PubMed  Google Scholar 

  • Ehrenreich H, tom Dieck K, Gefeller O, Kaw S, Schilling L, Poser W, Ruther E (1997) Sustained elevation of vasopressin plasma levels in healthy young men, but not in abstinent alcoholics, upon expectation of novelty. Psychoneuroendocrinology 22:13–24

    CAS  PubMed  Google Scholar 

  • Eisenhofer G, Johnson RH (1982) Effect of ethanol ingestion on plasma vasopressin and water balance in humans. Am J Phys 242:R522–R527

    CAS  Google Scholar 

  • Everts HG, Koolhaas JM (1999) Differential modulation of lateral septal vasopressin receptor blockade in spatial learning, social recognition, and anxiety-related behaviors in rats. Behav Brain Res 99:7–16

    CAS  PubMed  Google Scholar 

  • Fabio KM, Guillon CD, Lu SF, Heindel ND, Brownstein MJ, Lacey CJ, Garippa C, Simon NG (2013) Pharmacokinetics and metabolism of SRX246: a potent and selective vasopressin 1a antagonist. J Pharm Sci 102:2033–2043

    CAS  PubMed  Google Scholar 

  • Gill GV, Baylis PH, Flear CT, Skillen AW, Diggle PH (1982) Acute biochemical responses to moderate beer drinking. Br Med J (Clin Res Ed) 285:1770–1773

    CAS  Google Scholar 

  • Gillies GE, Linton EA, Lowry PJ (1982) Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin. Nature 299:355–357

    CAS  PubMed  Google Scholar 

  • Gray M, Innala L, Viau V (2012) Central vasopressin V1A receptor blockade impedes hypothalamic-pituitary-adrenal habituation to repeated restraint stress exposure in adult male rats. Neuropsychopharmacology 37:2712–2719

    CAS  PubMed  PubMed Central  Google Scholar 

  • Griebel G, Simiand J, Serradeil-Le Gal C, Wagnon J, Pascal M, Scatton B, Maffrand JP, Soubrie P (2002) Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci U S A 99:6370–6375

    CAS  PubMed  PubMed Central  Google Scholar 

  • Griebel G, Beeske S, Stahl SM (2012) The vasopressin V(1b) receptor antagonist SSR149415 in the treatment of major depressive and generalized anxiety disorders: results from 4 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry 73:1403–1411

    CAS  PubMed  Google Scholar 

  • Gulya K, Dave JR, Hoffman PL (1991) Chronic ethanol ingestion decreases vasopressin mRNA in hypothalamic and extrahypothalamic nuclei of mouse brain. Brain Res 557:129–135

    CAS  PubMed  Google Scholar 

  • Gulya K, Orpana AK, Sikela JM, Hoffman PL (1993) Prodynorphin and vasopressin mRNA levels are differentially affected by chronic ethanol ingestion in the mouse. Brain Res Mol Brain Res 20:1–8

    CAS  PubMed  Google Scholar 

  • Harding AJ, Halliday GM, Ng JL, Harper CG, Kril JJ (1996) Loss of vasopressin-immunoreactive neurons in alcoholics is dose-related and time-dependent. Neuroscience 72:699–708

    CAS  PubMed  Google Scholar 

  • Hasunuma I, Toyoda F, Okada R, Yamamoto K, Kadono Y, Kikuyama S (2013) Roles of arginine vasotocin receptors in the brain and pituitary of submammalian vertebrates. Int Rev Cell Mol Biol 304:191–225

    CAS  PubMed  Google Scholar 

  • Helderman JH, Vestal RE, Rowe JW, Tobin JD, Andres R, Robertson GL (1978) The response of arginine vasopressin to intravenous ethanol and hypertonic saline in man: the impact of aging. J Gerontol 33:39–47

    CAS  PubMed  Google Scholar 

  • Hernandez VS, Hernandez OR, Perez de la Mora M, Gomora MJ, Fuxe K, Eiden LE, Zhang L (2016) Hypothalamic vasopressinergic projections innervate central amygdala GABAergic neurons: implications for anxiety and stress coping. Front Neural Circuits 10:92

    PubMed  PubMed Central  Google Scholar 

  • Hernandez-Perez OR, Crespo-Ramirez M, Cuza-Ferrer Y, Anias-Calderon J, Zhang L, Roldan-Roldan G, Aguilar-Roblero R, Borroto-Escuela DO, Fuxe K, Perez de la Mora M (2018) Differential activation of arginine-vasopressin receptor subtypes in the amygdaloid modulation of anxiety in the rat by arginine-vasopressin. Psychopharmacology 235:1015–1027

    CAS  PubMed  Google Scholar 

  • Hillemacher T, Frieling H, Luber K, Yazici A, Muschler MA, Lenz B, Wilhelm J, Kornhuber J, Bleich S (2009) Epigenetic regulation and gene expression of vasopressin and atrial natriuretic peptide in alcohol withdrawal. Psychoneuroendocrinology 34:555–560

    CAS  PubMed  Google Scholar 

  • Hirasawa A, Hashimoto K, Tsujimoto G (1994) Distribution and developmental change of vasopressin V1A and V2 receptor mRNA in rats. Eur J Pharmacol 267:71–75

    CAS  PubMed  Google Scholar 

  • Hirschl MM, Derfler K, Bieglmayer C, Roggla H, Zeiner A, Seidler D, Laggner AN (1994) Hormonal derangements in patients with severe alcohol intoxication. Alcohol Clin Exp Res 18:761–766

    CAS  PubMed  Google Scholar 

  • Hodgson RA, Higgins GA, Guthrie DH, Lu SX, Pond AJ, Mullins DE, Guzzi MF, Parker EM, Varty GB (2007) Comparison of the V1b antagonist, SSR149415, and the CRF1 antagonist, CP-154,526, in rodent models of anxiety and depression. Pharmacol Biochem Behav 86:431–440

    CAS  PubMed  Google Scholar 

  • Hodgson RA, Mullins D, Lu SX, Guzzi M, Zhang X, Bleickardt CJ, Scott JD, Miller MW, Stamford AW, Parker EM, Varty GB (2014) Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior. Eur J Pharmacol 730:157–163

    CAS  PubMed  Google Scholar 

  • Hoffman PL (1982) Structural requirements for neurohypophyseal peptide maintenance of ethanol tolerance. Pharmacol Biochem Behav 17:685–690

    CAS  PubMed  Google Scholar 

  • Hoffman PL, Dave JR (1991) Chronic ethanol exposure uncouples vasopressin synthesis and secretion in rats. Neuropharmacology 30:1245–1249

    CAS  PubMed  Google Scholar 

  • Hoffman PL, Tabakoff B (1984) Neurohypophyseal peptides maintain tolerance to the incoordinating effects of ethanol. Pharmacol Biochem Behav 21:535–543

    CAS  PubMed  Google Scholar 

  • Hoffman PL, Ritzmann RF, Walter R, Tabakoff B (1978) Arginine vasopressin maintains ethanol tolerance. Nature 276:614–616

    CAS  PubMed  Google Scholar 

  • Hoorneman EM, Buijs RM (1982) Vasopressin fiber pathways in the rat brain following suprachiasmatic nucleus lesioning. Brain Res 243:235–241

    CAS  PubMed  Google Scholar 

  • Huber D, Veinante P, Stoop R (2005) Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 308:245–248

    CAS  PubMed  Google Scholar 

  • Hung CR, Tabakoff B, Melchior CL, Hoffman PL (1984) Intraventricular arginine vasopressin maintains ethanol tolerance. Eur J Pharmacol 106:645–648

    CAS  PubMed  Google Scholar 

  • Hwang BH, Froehlich JC, Hwang WS, Lumeng L, Li TK (1998) More vasopressin mRNA in the paraventricular hypothalamic nucleus of alcohol-preferring rats and high alcohol-drinking rats selectively bred for high alcohol preference. Alcohol Clin Exp Res 22:664–669

    CAS  PubMed  Google Scholar 

  • Iijima M, Yoshimizu T, Shimazaki T, Tokugawa K, Fukumoto K, Kurosu S, Kuwada T, Sekiguchi Y, Chaki S (2014) Antidepressant and anxiolytic profiles of newly synthesized arginine vasopressin V1B receptor antagonists: TASP0233278 and TASP0390325. Br J Pharmacol 171:3511–3525

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ishizawa H, Dave JR, Liu LI, Tabakoff B, Hoffman PL (1990) Hypothalamic vasopressin mRNA levels in mice are decreased after chronic ethanol ingestion. Eur J Pharmacol 189:119–127

    CAS  PubMed  Google Scholar 

  • Ishunina TA, Swaab DF (1999) Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex. J Clin Endocrinol Metab 84:4637–4644

    CAS  PubMed  Google Scholar 

  • Jahn H, Doring WK, Krampe H, Sieg S, Werner C, Poser W, Brunner E, Ehrenreich H (2004) Preserved vasopressin response to osmostimulation despite decreased basal vasopressin levels in long-term abstinent alcoholics. Alcohol Clin Exp Res 28:1925–1930

    CAS  PubMed  Google Scholar 

  • Kato Y, Igarashi N, Hirasawa A, Tsujimoto G, Kobayashi M (1995) Distribution and developmental changes in vasopressin V2 receptor mRNA in rat brain. Differentiation 59:163–169

    CAS  PubMed  Google Scholar 

  • Katz DA, Liu W, Locke C, Dutta S, Tracy KA (2016) Clinical safety and hypothalamic-pituitary-adrenal axis effects of the arginine vasopressin type 1B receptor antagonist ABT-436. Psychopharmacology 233:71–81

    CAS  PubMed  Google Scholar 

  • Katz DA, Locke C, Greco N, Liu W, Tracy KA (2017) Hypothalamic-pituitary-adrenal axis and depression symptom effects of an arginine vasopressin type 1B receptor antagonist in a one-week randomized phase 1b trial. Brain Behav 7:e00628

    PubMed  PubMed Central  Google Scholar 

  • Kornet M, Goosen C, Ribbens LG, Van Ree JM (1991) The effect of desglycinamide-(Arg8)-vasopressin (DGAVP) on the acquisition of free-choice alcohol drinking in rhesus monkeys. Alcohol Clin Exp Res 15:72–79

    CAS  PubMed  Google Scholar 

  • Kornet M, Goosen C, Thyssen JH, Van Ree JM (1992) Endocrine profile during acquisition of free-choice alcohol drinking in rhesus monkeys; treatment with desglycinamide-(Arg8)-vasopressin. Alcohol Alcohol 27:403–410

    CAS  PubMed  Google Scholar 

  • Landgraf R, Gerstberger R, Montkowski A, Probst JC, Wotjak CT, Holsboer F, Engelmann M (1995) V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci 15:4250–4258

    CAS  PubMed  Google Scholar 

  • Le AD, Kalant H, Khanna JM (1982) Interaction between des-glycinamide9-[Arg8] vasopressin and serotonin on ethanol tolerance. Eur J Pharmacol 80:337–345

    CAS  PubMed  Google Scholar 

  • Lee MR, Weerts EM (2016) Oxytocin for the treatment of drug and alcohol use disorders. Behav Pharmacol 27:640–648

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liebsch G, Wotjak CT, Landgraf R, Engelmann M (1996) Septal vasopressin modulates anxiety-related behaviour in rats. Neurosci Lett 217:101–104

    CAS  PubMed  Google Scholar 

  • Linkola J, Fyhrquist F (1978) Urinary cyclic AMP and vasopressin excretion in rat strains selected for their alcohol intake. Acta Physiol Scand 102:364–367

    CAS  PubMed  Google Scholar 

  • Linkola J, Fyhrquist F, Forsander O (1977) Effects of ethanol on urinary arginine vasopressin excretion in two rat strains selected for their different ethanol preferences. Acta Physiol Scand 101:126–128

    CAS  PubMed  Google Scholar 

  • Linkola J, Ylikahri R, Fyhquist F, Wallenius M (1978) Plasma vasopressin in ethanol intoxication and hangover. Acta Physiol Scand 104:180–187

    CAS  PubMed  Google Scholar 

  • Litten RZ, Egli M, Heilig M, Cui C, Fertig JB, Ryan ML, Falk DE, Moss H, Huebner R, Noronha A (2012) Medications development to treat alcohol dependence: a vision for the next decade. Addict Biol 17:513–527

    CAS  PubMed  PubMed Central  Google Scholar 

  • Litvin Y, Murakami G, Pfaff DW (2011) Effects of chronic social defeat on behavioral and neural correlates of sociality: vasopressin, oxytocin and the vasopressinergic V1b receptor. Physiol Behav 103:393–403

    CAS  PubMed  Google Scholar 

  • Lolait SJ, Stewart LQ, Jessop DS, Young WS 3rd, O’Carroll AM (2007a) The hypothalamic-pituitary-adrenal axis response to stress in mice lacking functional vasopressin V1b receptors. Endocrinology 148:849–856

    CAS  PubMed  Google Scholar 

  • Lolait SJ, Stewart LQ, Roper JA, Harrison G, Jessop DS, Young WS 3rd, O’Carroll AM (2007b) Attenuated stress response to acute lipopolysaccharide challenge and ethanol administration in vasopressin V1b receptor knockout mice. J Neuroendocrinol 19:543–551

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ma XM, Lightman SL (1998) The arginine vasopressin and corticotrophin-releasing hormone gene transcription responses to varied frequencies of repeated stress in rats. J Physiol 510(Pt 2):605–614

    CAS  PubMed  PubMed Central  Google Scholar 

  • Madeira MD, Andrade JP, Lieberman AR, Sousa N, Almeida OF, Paula-Barbosa MM (1997) Chronic alcohol consumption and withdrawal do not induce cell death in the suprachiasmatic nucleus, but lead to irreversible depression of peptide immunoreactivity and mRNA levels. J Neurosci 17:1302–1319

    CAS  PubMed  Google Scholar 

  • Maher BS, Vladimirov VI, Latendresse SJ, Thiselton DL, McNamee R, Kang M, Bigdeli TB, Chen X, Riley BP, Hettema JM, Chilcoat H, Heidbreder C, Muglia P, Murrelle EL, Dick DM, Aliev F, Agrawal A, Edenberg HJ, Kramer J, Nurnberger J, Tischfield JA, Devlin B, Ferrell RE, Kirillova GP, Tarter RE, Kendler KS, Vanyukov MM (2011) The AVPR1A gene and substance use disorders: association, replication, and functional evidence. Biol Psychiatry 70:519–527

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mak P, Broussard C, Vacy K, Broadbear JH (2012) Modulation of anxiety behavior in the elevated plus maze using peptidic oxytocin and vasopressin receptor ligands in the rat. J Psychopharmacol 26:532–542

    CAS  PubMed  Google Scholar 

  • Makino S, Smith MA, Gold PW (1995) Increased expression of corticotropin-releasing hormone and vasopressin messenger ribonucleic acid (mRNA) in the hypothalamic paraventricular nucleus during repeated stress: association with reduction in glucocorticoid receptor mRNA levels. Endocrinology 136:3299–3309

    CAS  PubMed  Google Scholar 

  • Mander AJ, Young A, Merrick MV, Morton JJ (1989) Fluid balance, vasopressin and withdrawal symptoms during detoxification from alcohol. Drug Alcohol Depend 24:233–237

    CAS  PubMed  Google Scholar 

  • Mannix SA, Hoffman PL, Melchior CL (1986) Intraventricular arginine vasopressin blocks the acquisition of ethanol tolerance in mice. Eur J Pharmacol 128:137–141

    CAS  PubMed  Google Scholar 

  • McBride WJ (2002) Central nucleus of the amygdala and the effects of alcohol and alcohol-drinking behavior in rodents. Pharmacol Biochem Behav 71:509–515

    CAS  PubMed  Google Scholar 

  • Melchior CL, Tabakoff B (1985) Features of environment-dependent tolerance to ethanol. Psychopharmacology 87:94–100

    CAS  PubMed  Google Scholar 

  • Milik E, Szczepanska-Sadowska E, Dobruch J, Cudnoch-Jedrzejewska A, Maslinski W (2014) Altered expression of V1a receptors mRNA in the brain and kidney after myocardial infarction and chronic stress. Neuropeptides 48:257–266

    CAS  PubMed  Google Scholar 

  • Moritoh S, Sato K, Okada Y, Koizumi A (2011) Endogenous arginine vasopressin-positive retinal cells in arginine vasopressin-eGFP transgenic rats identified by immunohistochemistry and reverse transcriptase-polymerase chain reaction. Mol Vis 17:3254–3261

    CAS  PubMed  PubMed Central  Google Scholar 

  • Murgatroyd C, Wigger A, Frank E, Singewald N, Bunck M, Holsboer F, Landgraf R, Spengler D (2004) Impaired repression at a vasopressin promoter polymorphism underlies overexpression of vasopressin in a rat model of trait anxiety. J Neurosci 24:7762–7770

    CAS  PubMed  Google Scholar 

  • Nakamura K, Fujiwara Y, Mizutani R, Sanbe A, Miyauchi N, Hiroyama M, Yamauchi J, Yamashita T, Nakamura S, Mori T, Tsujimoto G, Tanoue A (2008) Effects of vasopressin V1b receptor deficiency on adrenocorticotropin release from anterior pituitary cells in response to oxytocin stimulation. Endocrinology 149:4883–4891

    CAS  PubMed  Google Scholar 

  • Naughton M (2016) Electrophysiological study of the effects of arginine vasopressin in the rat juxtacapsular nucleus of the bed nucleus of the stria terminalis. Queen’s University (Canada)

  • Nelson BS, Sequeira MK, Schank JR (2018) Bidirectional relationship between alcohol intake and sensitivity to social defeat: association with Tacr1 and Avp expression. Addict Biol 23:142–153

    CAS  PubMed  Google Scholar 

  • Neumann ID, Landgraf R (2012) Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci 35:649–659

    CAS  PubMed  Google Scholar 

  • Ogilvie KM, Lee S, Rivier C (1997) Role of arginine vasopressin and corticotropin-releasing factor in mediating alcohol-induced adrenocorticotropin and vasopressin secretion in male rats bearing lesions of the paraventricular nuclei. Brain Res 744:83–95

    CAS  PubMed  Google Scholar 

  • Otero-Garcia M, Martin-Sanchez A, Fortes-Marco L, Martinez-Ricos J, Agustin-Pavon C, Lanuza E, Martinez-Garcia F (2014) Extending the socio-sexual brain: arginine-vasopressin immunoreactive circuits in the telencephalon of mice. Brain Struct Funct 219:1055–1081

    CAS  PubMed  Google Scholar 

  • Otero-Garcia M, Agustin-Pavon C, Lanuza E, Martinez-Garcia F (2016) Distribution of oxytocin and co-localization with arginine vasopressin in the brain of mice. Brain Struct Funct 221:3445–3473

    CAS  PubMed  Google Scholar 

  • Overstreet DH, Griebel G (2005) Antidepressant-like effects of the vasopressin V1b receptor antagonist SSR149415 in the Flinders sensitive line rat. Pharmacol Biochem Behav 82:223–227

    CAS  PubMed  Google Scholar 

  • Overstreet DH, Knapp DJ, Breese GR (2002) Accentuated decrease in social interaction in rats subjected to repeated ethanol withdrawals. Alcohol Clin Exp Res 26:1259–1268

    PubMed  PubMed Central  Google Scholar 

  • Pak TR, Chung WC, Hinds LR, Handa RJ (2009) Arginine vasopressin regulation in pre- and postpubertal male rats by the androgen metabolite 3beta-diol. Am J Phys Endocrinol Metab 296:E1409–E1413

    CAS  Google Scholar 

  • Pan Y, Liu Y, Young KA, Zhang Z, Wang Z (2009) Post-weaning social isolation alters anxiety-related behavior and neurochemical gene expression in the brain of male prairie voles. Neurosci Lett 454:67–71

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paula-Barbosa MM, Silva SM, Andrade JP, Cadete-Leite A, Madeira MD (2001) Nerve growth factor restores mRNA levels and the expression of neuropeptides in the suprachiasmatic nucleus of rats submitted to chronic ethanol treatment and withdrawal. J Neurocytol 30:195–207

    CAS  PubMed  Google Scholar 

  • Pedersen CA, Smedley KL, Leserman J, Jarskog LF, Rau SW, Kampov-Polevoi A, Casey RL, Fender T, Garbutt JC (2013) Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcohol Clin Exp Res 37:484–489

    CAS  PubMed  Google Scholar 

  • Pinnock SB, Herbert J (2001) Corticosterone differentially modulates expression of corticotropin releasing factor and arginine vasopressin mRNA in the hypothalamic paraventricular nucleus following either acute or repeated restraint stress. Eur J Neurosci 13:576–584

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rabadan-Diehl C, Lolait SJ, Aguilera G (1995) Regulation of pituitary vasopressin V1b receptor mRNA during stress in the rat. J Neuroendocrinol 7:903–910

    CAS  PubMed  Google Scholar 

  • Raggenbass M (2008) Overview of cellular electrophysiological actions of vasopressin. Eur J Pharmacol 583:243–254

    CAS  PubMed  Google Scholar 

  • Ramanathan G, Cilz NI, Kurada L, Hu B, Wang X, Lei S (2012) Vasopressin facilitates GABAergic transmission in rat hippocampus via activation of V(1A) receptors. Neuropharmacology 63:1218–1226

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rigter H, Dortmans C, Crabbe JC Jr (1980a) Effects of peptides related to neurohypophyseal hormones on ethanol tolerance. Pharmacol Biochem Behav 13(Suppl 1):285–290

    CAS  PubMed  Google Scholar 

  • Rigter H, Rijk H, Crabbe JC (1980b) Tolerance to ethanol and severity of withdrawal in mice are enhanced by a vasopressin fragment. Eur J Pharmacol 64:53–68

    CAS  PubMed  Google Scholar 

  • Rivier C, Lee S (1996) Acute alcohol administration stimulates the activity of hypothalamic neurons that express corticotropin-releasing factor and vasopressin. Brain Res 726:1–10

    CAS  PubMed  Google Scholar 

  • Rodriguez-Borrero E, Rivera-Escalera F, Candelas F, Montalvo J, Munoz-Miranda WJ, Walker JR, Maldonado-Vlaar CS (2010) Arginine vasopressin gene expression changes within the nucleus accumbens during environment elicited cocaine-conditioned response in rats. Neuropharmacology 58:88–101

    CAS  PubMed  Google Scholar 

  • Rood BD, Beck SG (2014) Vasopressin indirectly excites dorsal raphe serotonin neurons through activation of the vasopressin1A receptor. Neuroscience 260:205–216

    CAS  PubMed  Google Scholar 

  • Rood BD, De Vries GJ (2011) Vasopressin innervation of the mouse (Mus musculus) brain and spinal cord. J Comp Neurol 519:2434–2474

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rood BD, Stott RT, You S, Smith CJ, Woodbury ME, De Vries GJ (2013) Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain. J Comp Neurol 521:2321–2358

    CAS  PubMed  Google Scholar 

  • Roper JA, Craighead M, O’Carroll AM, Lolait SJ (2010) Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist. J Neuroendocrinol 22:1173–1180

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ryan ML, Falk DE, Fertig JB, Rendenbach-Mueller B, Katz DA, Tracy KA, Strain EC, Dunn KE, Kampman K, Mahoney E, Ciraulo DA, Sickles-Colaneri L, Ait-Daoud N, Johnson BA, Ransom J, Scott C, Koob GF, Litten RZ (2017) A phase 2, double-blind, placebo-controlled randomized trial assessing the efficacy of ABT-436, a novel V1b receptor antagonist, for alcohol dependence. Neuropsychopharmacology 42:1012–1023

    CAS  PubMed  Google Scholar 

  • Salome N, Stemmelin J, Cohen C, Griebel G (2006) Differential roles of amygdaloid nuclei in the anxiolytic- and antidepressant-like effects of the V1b receptor antagonist, SSR149415, in rats. Psychopharmacology (Berlin) 187:237–244

    CAS  Google Scholar 

  • Sanbe A, Takagi N, Fujiwara Y, Yamauchi J, Endo T, Mizutani R, Takeo S, Tsujimoto G, Tanoue A (2008) Alcohol preference in mice lacking the Avpr1a vasopressin receptor. Am J Physiol Regul Integr Comp Physiol 294:R1482–R1490

    CAS  PubMed  Google Scholar 

  • Sanna PP, Folsom DP, Barizo MJ, Hirsch MD, Melia KR, Maciejewski-Lenoir D, Bloom FE (1993) Chronic ethanol intake decreases vasopressin mRNA content in the rat hypothalamus: a PCR study. Brain Res Mol Brain Res 19:241–245

    CAS  PubMed  Google Scholar 

  • Sawchenko PE, Arias CA, Mortrud MT (1993) Local tetrodotoxin blocks chronic stress effects on corticotropin-releasing factor and vasopressin messenger ribonucleic acids in hypophysiotropic neurons. J Neuroendocrinol 5:341–348

    CAS  PubMed  Google Scholar 

  • Schreiber AL, Gilpin NW (2018) Corticotropin-releasing factor (CRF) neurocircuitry and neuropharmacology in alcohol drinking. Handb Exp Pharmacol

  • Serradeil-Le Gal C, Wagnon J, Simiand J, Griebel G, Lacour C, Guillon G, Barberis C, Brossard G, Soubrie P, Nisato D, Pascal M, Pruss R, Scatton B, Maffrand JP, Le Fur G (2002) Characterization of (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist. J Pharmacol Exp Ther 300:1122–1130

    CAS  PubMed  Google Scholar 

  • Shimazaki T, Iijima M, Chaki S (2006) The pituitary mediates the anxiolytic-like effects of the vasopressin V1B receptor antagonist, SSR149415, in a social interaction test in rats. Eur J Pharmacol 543:63–67

    CAS  PubMed  Google Scholar 

  • Silva SM, Paula-Barbosa MM, Madeira MD (2002) Prolonged alcohol intake leads to reversible depression of corticotropin-releasing hormone and vasopressin immunoreactivity and mRNA levels in the parvocellular neurons of the paraventricular nucleus. Brain Res 954:82–93

    CAS  PubMed  Google Scholar 

  • Sinha R (2007) The role of stress in addiction relapse. Curr Psychiatry Rep 9:388–395

    PubMed  Google Scholar 

  • Smith CJ, Poehlmann ML, Li S, Ratnaseelan AM, Bredewold R, Veenema AH (2017) Age and sex differences in oxytocin and vasopressin V1a receptor binding densities in the rat brain: focus on the social decision-making network. Brain Struct Funct 222:981–1006

    CAS  PubMed  Google Scholar 

  • Sofroniew MV (1980) Projections from vasopressin, oxytocin, and neurophysin neurons to neural targets in the rat and human. J Histochem Cytochem 28:475–478

    CAS  PubMed  Google Scholar 

  • Sofroniew MV (1983) Morphology of vasopressin and oxytocin neurones and their central and vascular projections. Prog Brain Res 60:101–114

    CAS  PubMed  Google Scholar 

  • Sofroniew MV (1985) Vasopressin- and neurophysin-immunoreactive neurons in the septal region, medial amygdala and locus coeruleus in colchicine-treated rats. Neuroscience 15:347–358

    CAS  PubMed  Google Scholar 

  • Sofroniew MV, Weindl A (1978) Projections from the parvocellular vasopressin- and neurophysin-containing neurons of the suprachiasmatic nucleus. Am J Anat 153:391–429

    CAS  PubMed  Google Scholar 

  • Song Z, Albers HE (2017) Cross-talk among oxytocin and arginine-vasopressin receptors: relevance for basic and clinical studies of the brain and periphery. Front Neuroendocrinol

  • Sousa N, Madeira MD, Ruela C, Paula-Barbosa MM (1995) Structural reorganization in the supraoptic nucleus of withdrawn rats following long-term alcohol consumption. Alcohol Clin Exp Res 19:879–885

    CAS  PubMed  Google Scholar 

  • Spierling SR, Zorrilla EP (2017) Don’t stress about CRF: assessing the translational failures of CRF1antagonists. Psychopharmacology 234:1467–1481

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stemmelin J, Lukovic L, Salome N, Griebel G (2005) Evidence that the lateral septum is involved in the antidepressant-like effects of the vasopressin V1b receptor antagonist, SSR149415. Neuropsychopharmacology 30:35–42

    CAS  PubMed  Google Scholar 

  • Stevenson EL, Caldwell HK (2012) The vasopressin 1b receptor and the neural regulation of social behavior. Horm Behav 61:277–282

    CAS  PubMed  Google Scholar 

  • Stoop R (2012) Neuromodulation by oxytocin and vasopressin. Neuron 76:142–159

    CAS  PubMed  Google Scholar 

  • Szabo G, Tabakoff B, Hoffman PL (1988) Receptors with V1 characteristics mediate the maintenance of ethanol tolerance by vasopressin. J Pharmacol Exp Ther 247:536–541

    CAS  PubMed  Google Scholar 

  • Szot P, Bale TL, Dorsa DM (1994) Distribution of messenger RNA for the vasopressin V1a receptor in the CNS of male and female rats. Brain Res Mol Brain Res 24:1–10

    CAS  PubMed  Google Scholar 

  • Taivainen H, Laitinen K, Tahtela R, Kilanmaa K, Valimaki MJ (1995) Role of plasma vasopressin in changes of water balance accompanying acute alcohol intoxication. Alcohol Clin Exp Res 19:759–762

    CAS  PubMed  Google Scholar 

  • Terranova JI, Ferris CF, Albers HE (2017) Sex differences in the regulation of offensive aggression and dominance by arginine-vasopressin. Front Endocrinol (Lausanne) 8:308

    Google Scholar 

  • Thiagarajan AB, Mefford IN, Eskay RL (1989) Single-dose ethanol administration activates the hypothalamic-pituitary-adrenal axis: exploration of the mechanism of action. Neuroendocrinology 50:427–432

    CAS  PubMed  Google Scholar 

  • Thomas A, Kim NB, Amico JA (1996) Sequential exposure to estrogen and testosterone (T) and subsequent withdrawal of T increases the level of arginine vasopressin messenger ribonucleic acid in the hypothalamic paraventricular nucleus of the female rat. J Neuroendocrinol 8:793–800

    CAS  PubMed  Google Scholar 

  • Thompson RR, George K, Walton JC, Orr SP, Benson J (2006) Sex-specific influences of vasopressin on human social communication. Proc Natl Acad Sci U S A 103:7889–7894

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tobin VA, Hashimoto H, Wacker DW, Takayanagi Y, Langnaese K, Caquineau C, Noack J, Landgraf R, Onaka T, Leng G, Meddle SL, Engelmann M, Ludwig M (2010) An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 464:413–417

    CAS  PubMed  PubMed Central  Google Scholar 

  • Trabert W, Caspari D, Bernhard P, Biro G (1992) Inappropriate vasopressin secretion in severe alcohol withdrawal. Acta Psychiatr Scand 85:376–379

    CAS  PubMed  Google Scholar 

  • van Leeuwen FW, Caffe AR, De Vries GJ (1985) Vasopressin cells in the bed nucleus of the stria terminalis of the rat: sex differences and the influence of androgens. Brain Res 325:391–394

    PubMed  Google Scholar 

  • Veinante P, Freund-Mercier MJ (1997) Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J Comp Neurol 383:305–325

    CAS  PubMed  Google Scholar 

  • Walter R, Hoffman PL, Flexner JB, Flexner LB (1975) Neurohypophyseal hormones, analogs, and fragments: their effect on puromycin-induced amnesia. Proc Natl Acad Sci U S A 72:4180–4184

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wersinger SR, Ginns EI, O’Carroll AM, Lolait SJ, Young WS 3rd (2002) Vasopressin V1b receptor knockout reduces aggressive behavior in male mice. Mol Psychiatry 7:975–984

    CAS  PubMed  Google Scholar 

  • Whitnall MH, Mezey E, Gainer H (1985) Co-localization of corticotropin-releasing factor and vasopressin in median eminence neurosecretory vesicles. Nature 317:248–250

    CAS  PubMed  Google Scholar 

  • Winslow JT, Hastings N, Carter CS, Harbaugh CR, Insel TR (1993) A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365:545–548

    CAS  PubMed  Google Scholar 

  • Young WS, Li J, Wersinger SR, Palkovits M (2006) The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy. Neuroscience 143:1031–1039

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Kreek MJ (2018) Involvement of activated brain stress responsive systems in excessive and “relapse” alcohol drinking in rodent models: implications for therapeutics. J Pharmacol Exp Ther 366:9–20

    CAS  PubMed  Google Scholar 

  • Zhou L, Blaustein JD, De Vries GJ (1994) Distribution of androgen receptor immunoreactivity in vasopressin- and oxytocin-immunoreactive neurons in the male rat brain. Endocrinology 134:2622–2627

    CAS  PubMed  Google Scholar 

  • Zhou Y, Colombo G, Carai MA, Ho A, Gessa GL, Kreek MJ (2011) Involvement of arginine vasopressin and V1b receptor in alcohol drinking in Sardinian alcohol-preferring rats. Alcohol Clin Exp Res 35:1876–1883

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Rubinstein M, Low MJ, Kreek MJ (2018) V1b receptor antagonist SSR149415 and naltrexone synergistically decrease excessive alcohol drinking in male and female mice. Alcohol Clin Exp Res 42:195–205

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Fulton Crews for his comments on this manuscript.

Funding

This work was supported in part by the Bowles Center for Alcohol Studies and the National Institute on Alcoholism and Alcohol Abuse (P60AA01165; R01AA022234; R01AA021275).

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

    Kathryn M. Harper, Darin J. Knapp, Hugh E. Criswell & George R. Breese

  2. Department of Psychiatry, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7178, USA

    Darin J. Knapp, Hugh E. Criswell & George R. Breese

  3. Department of Pharmacology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599-7178, USA

    George R. Breese

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  1. Kathryn M. Harper
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Harper, K.M., Knapp, D.J., Criswell, H.E. et al. Vasopressin and alcohol: a multifaceted relationship. Psychopharmacology 235, 3363–3379 (2018). https://doi.org/10.1007/s00213-018-5099-x

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Keywords

  • Ethanol
  • Vasopressin
  • Hypothalamus
  • Amygdala
  • Anxiety
  • Alcohol intake
  • Tolerance
  • Clinical trials
  • Antagonists
  • Stress