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Negative relationship between brain α1A-AR neurotransmission and βArr2 levels in anxious adolescent rats subjected to early life stress

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Abstract

Early-life stress is correlated with the development of anxiety-related behavior in adolescence, but underlying mechanisms remain poorly known. The α1A-adrenergic receptor (AR) is linked to mood regulation and its function is assumed to be regulated by β-arrestins (βArrs) via desensitization and downregulation. Here, we investigated correlation between changes in α1A-AR and βArr2 levels in the prefrontal cortex (PFC) and hippocampus of adolescent and adult male rats subjected to maternal separation (MS) and their relationship with anxiety-like behavior in adolescence. MS was performed 3 h per day from postnatal days 2–11 and anxiety-like behavior was evaluated in the elevated plus-maze and open field tests. The protein levels were examined using western blot assay. MS decreased α1A-AR expression and increased βArr2 expression in both brain regions of adolescent rats, while induced reverse changes in adulthood. MS adolescent rats demonstrated higher anxiety-type behavior and lower activity in behavioral tests than controls. Decreased α1A-AR levels in MS adolescence strongly correlated with reduced time spent in the open field central area, consistent with increased anxiety-like behavior. An anxiety-like phenotype was mimicked by acute and chronic treatment of developing rats with prazosin, an α1A-AR antagonist, suggesting α1A-AR downregulation may facilitate anxiety behavior in MS adolescent rats. Together, our results indicate a negative correlation between α1A-AR neurotransmission and βArr2 levels in both adults and anxious-adolescent rats and suggest that increased βArr2 levels may contribute to posttranslational regulation of α1A-AR and modulation of anxiety-like behavior in adolescent rats. This may provide a path to develop more effective anxiolytic treatments.

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Abbreviations

PFC:

Prefrontal cortex

AR:

Adrenergic receptor

GPCR:

G protein-coupled receptor

MS:

Maternal separation

βArr:

β-Arrestin

EPM:

Elevated plus-maze

OF:

Open field

PZ:

Prazosin

References

  • Arnsten AF, Raskind MA, Taylor FB, Connor DF (2015) The effects of stress exposure on prefrontal cortex: translating basic research into successful treatments for post-traumatic stress disorder. Neurobiol Stress 1:89–99

    Google Scholar 

  • Asth L, Ruzza C, Malfacini D, Medeiros I, Guerrini R, Zaveri NT, Gavioli EC, Calo G (2016) Beta-arrestin 2 rather than G protein efficacy determines the anxiolytic-versus antidepressant-like effects of nociceptin/orphanin FQ receptor ligands. Neuropharmacology 105:434–442

    CAS  Google Scholar 

  • Benovic JL, Kühn H, Weyand I, Codina J, Caron MG, Lefkowitz RJ (1987) Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc Natl Acad Sci U S A 84:8879–8882

    CAS  Google Scholar 

  • Bjork K, Rimondini R, Hansson AC, Terasmaa A, Hyytia P, Heilig M, Sommer WH (2008) Modulation of voluntary ethanol consumption by beta-arrestin 2. FASEB J 22:2552–2560

    CAS  Google Scholar 

  • Blanc R, Ville A, Glowinski J, Tassin J (2002) Critical role of a1-adrenergic receptors in acute and sensitized locomotor effects of D-amphetamine, cocaine, and GBR12783: influence of preexposure conditions and pharmacological characteristics. Synapse 43:51–61

    Google Scholar 

  • Bondar NP, Merkulova TI (2016) Brain-derived neurotrophic factor and early-life stress: multifaceted interplay. J Biosci 41:751–758

    CAS  Google Scholar 

  • Bylund DB, Reed AL (2007) Childhood and adolescent depression: why do children and adults respond differently to antidepressant drugs? Neurochem Int 51:246–253

    CAS  Google Scholar 

  • Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, Joëls M, Krugers H (2008) Maternal care and hippocampal plasticity: evidence for experience-dependent structural plasticity, altered synaptic functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci 28:6037–6045

    CAS  Google Scholar 

  • Chiang T, Sansuk K, van Rijn RM (2016) beta-Arrestin 2 dependence of delta opioid receptor agonists is correlated with alcohol intake. Br J Pharmacol 173:332–343

    CAS  Google Scholar 

  • Chocyk A, Bobula B, Dudys D, Przyborowska A, Majcher-Maślanka I, Hess G, Wędzony K (2013) Early-life stress affects the structural and functional plasticity of the medial prefrontal cortex in adolescent rats. Eur J Neurosci 38:2089–2107

    Google Scholar 

  • Coccurello R, Bielawski A, Zelek-Molik A, Vetulani J, Kowalska M, D’Amato FR, Nalepa I (2014) Brief maternal separation affects brain α1-adrenoceptors and apoptotic signaling in adult mice. Prog Neuropsychopharmacol Biol Psychiatry 48:161–169

    CAS  Google Scholar 

  • Collier TJ, Greene JG, Felten DL, Stevens SY, Steece K (2004) Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats. Neurobiol Aging 25:209–221

    CAS  Google Scholar 

  • Coyle JT, Duman RS (2003) Finding the intracellular signaling pathways affected by mood disorder treatments. Neuron 38:157–160

    CAS  Google Scholar 

  • Danese A, McEwen BS (2012) Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav 106:29–39

    CAS  Google Scholar 

  • Deupree JD, Reed AL, Bylund DB (2007) Differential effects of the tricyclic antidepressant desipramine on the density of adrenergic receptors in juvenile and adult rats. J Pharmacol Exp Ther 321(2):770–776

    CAS  Google Scholar 

  • Ding J, Han F, Wen L, Xiao B, Shi Y (2017) The role of β-arrestin-2 on Fear/anxious-related memory in a rat model of Post-traumatic stress disorder. J Affect Disord 213:1–8

    Google Scholar 

  • Do-Monte FHM, Melody Allensworth M, Carobrez AP (2010) Impairment of contextual conditioned fear extinction after microinjection of alpha-1-adrenergic blocker prazosin into the medial prefrontal cortex. Behav Brain Res 211:89–95

    CAS  Google Scholar 

  • Doze VA, Handel EM, Jensen KA, Darsie B, Luger EJ, Haselton JR, Talbot JN, Rorabaugh BR (2009) a1A- and a1B adrenergic receptors differentially modulate antidepressant-like behavior in the mouse. Brain Res 1285:148–157

    CAS  Google Scholar 

  • Ferguson SA, Cada AM (2003) A longitudinal study of short- and long-term activity levels in male and female spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats. Behav Neurosci 117:271–282

    Google Scholar 

  • Fillion T, Blass E (1986) Infantile experience with suckling odors determines adult sexual behavior in male rats. Science 231:729–731

    CAS  Google Scholar 

  • Finch AM, Sarramegna V, Graham RM (2006) Ligand Binding, Activation, and Agonist Trafficking. In: Perez DM (ed) The Adrenergic Receptors. The Receptors. Humana Press

  • Funk D, Coen K, Tamadon S, Le AD (2019) Effects of the alpha-1 antagonist prazosin on KOR agonist-induced reinstatement of alcohol seeking. Int J Neuropsychopharmacol 22:724–734

    CAS  Google Scholar 

  • Gainetdinov RR, Premont RT, Bohn LM, Lefkowitz RJ, Caron MG (2004) Desensitization of G protein-coupled receptors and neuronal functions. Annu Rev Neurosci 27:107–144

    CAS  Google Scholar 

  • Gentsch C, Lichtsteiner M, Feer H (1987) Open field and elevated plus-maze: a between, open field and elevated plus-maze: a behavioural comparison between spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats and the effects of chlordiazepoxide. Behav Brain Res 25:101–107

    CAS  Google Scholar 

  • Goddard AW, Ball SG, Martinez J, Robinson MJ, Yang CR, Russell JM, Shekhar A (2010) Current perspectives of the roles of the central norepinephrine system in anxiety and depression. Depress Anxiety 27:339–350

    CAS  Google Scholar 

  • Hahn YK, Paris JJ, Lichtman AH, Hauser KF, Sim-Selley LJ, Selley DE, Selley DE, Knapp PE (2016) Central HIV-1 Tat exposure elevates anxiety and fear conditioned responses of male mice concurrent with altered mu-opioid receptor-mediated G-protein activation and β-arrestin 2 activity in the forebrain. Neurobiol Dis 92:124–136

    CAS  Google Scholar 

  • Heim C, Plotsky PM, Nemeroff CB (2004) Importance of studying the contributions of early adverse experience to neurobiological findings in depression. Neuropsychopharmacology 29:641–648

    Google Scholar 

  • Hennenberg M, Schlenker B, Roosen A, Strittmatter F, Walther S, Stief C, Gratzke C (2011) β-arrestin-2 is expressed in human prostate smooth muscle and a binding partner of α1A-adrenoceptors. World J Urol 29:157–163

    CAS  Google Scholar 

  • Herpfer I, Hezel H, Reichardt W, Clark K, Geiger J, Gross CM, Heyer A, Neagu V, Bhatia H, Atas HC, Fiebich BL, Bischofberger J, Haas CA, Lieb K, Normann C (2012) Early life stress differentially modulates distinct forms of brain plasticity in young and adult mice. PLoS ONE 7:e46004

    CAS  Google Scholar 

  • Hill AS, Sahay A, Hen R (2015) Increasing adult hippocampal neurogenesis is sufficient to reduce anxiety and depression-like behaviors. Neuropsychopharmacology 40(10):2368–2378

    CAS  Google Scholar 

  • Howells FM, Russell VA (2008) Glutamate-stimulated release of norepinephrine in hippocampal slices of animal models of attention-deficit/hyperactivity disorder (spontaneously hypertensive rat) and depression/anxiety-like behaviours (Wistar–Kyoto rat). Brain Res 1200:107–115

    CAS  Google Scholar 

  • Howells FM, Stein DJ, Russell VA (2012) Synergistic tonic and phasic activity of the locus coeruleus norepinephrine (LC-NE) arousal system is required for optimal attentional performance. Metab Brain Dis 27:267–274

    CAS  Google Scholar 

  • Janthakhin Y, Rincel M, Costa AM, Darnaudery M, Ferreira G (2017) Maternal high-fat diet leads to hippocampal and amygdala dendritic remodeling in adult male offspring. Psychoneuroendocrinology 83:49–57

    CAS  Google Scholar 

  • Jean-Charles PY, Kaur S, Shenoy SK (2017) G Protein-coupled receptor signaling through β-arrestin-dependent mechanisms. J Cardiovasc Pharmacol 70:142–158

    CAS  Google Scholar 

  • Jin S, Zhao Y, Jiang Y, Wang Y, Li C, Zhang D, Lian B, Du Z, Sun H, Sun L (2018) Anxiety-like behaviour assessments of adolescent rats after repeated maternal separation during early life. NeuroReport 29:643–649

    Google Scholar 

  • Johnson JG, Cohen P, Gould MS, Kasen S, Brown J, Brook JS (2002) Childhood adversities, interpersonal difficulties, and risk for suicide attempts during late adolescence and early adulthood. Arch Gen Psychiatry 59:741–749

    Google Scholar 

  • Kessler RC, Avenevoli S, Costello EJ, Georgiades K, Green JG, Gruber MJ, He JP, Koretz D, McLaughlin KA, Petukhova M, Sampson NA, Zaslavsky AM, Merikangas KR (2012) Prevalence, persistence, and sociodemographic correlates of DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement. Arch Gen Psychiatry 69:372–380

    Google Scholar 

  • Kim EJ, Pellman B, Kim JJ (2015) Stress effects on the hippocampus: a critical review. Learn Mem 22:411–416

    Google Scholar 

  • Krasel C, Bünemann M, Lorenz K, Lohse MJ (2005) Beta-arrestin binding to the beta2-adrenergic receptor requires both receptor phosphorylation and receptor activation. J Biol Chem 280:9528–9535

    CAS  Google Scholar 

  • Krugers HJ, Joels M (2014) Long-lasting consequences of early life stress on brain structure, emotion and cognition. Curr Top Behav Neurosci 18:81–92

    CAS  Google Scholar 

  • Laporte SA, Miller WE, Kim KM, Caron MG (2002) beta-Arrestin/AP-2 interaction in G protein-coupled receptor internalization: identification of a beta-arrestin binging site in beta 2-adaptin. J Biol Chem 277:9247–9254

    CAS  Google Scholar 

  • Lefkowitz RG (1998) G protein-coupled receptors. III. New roles for receptor kinases and beta-arrestins in receptor signaling and desensitization. J Biol Chem 273:18677–18680

    CAS  Google Scholar 

  • Lefkowitz RJ, Shenoy SK (2005) Transduction of receptor signals by beta-arrestins. Science 308:512–517

    CAS  Google Scholar 

  • Li Y, Li H, Liu X, Bao G, Tao Y, Wu Z, Xia P, Wu C, Li B, Ma L (2009) Regulation of amygdalar PKA by beta-arrestin-2/phosphodiesterase-4 complex is critical for fear conditioning. Proc Natl Acad Sci U S A 106:21918–21923

    CAS  Google Scholar 

  • Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (1990) beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 248:1547–1550

    CAS  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    CAS  Google Scholar 

  • Mc Fie S, Sterley TL, Howells FM, Russell VA (2012) Clozapine decreases exploratory activity and increases anxiety-like behaviour in the Wistar-Kyoto rat but not the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder. Brain Res 1467:91–103

    CAS  Google Scholar 

  • Moriceau S, Shionoya K, Jakubs K, Sullivan RM (2009) Early-life stress disrupts attachment learning: the role of amygdala corticosterone, locus ceruleus corticotropin releasing hormone, and olfactory bulb norepinephrine. J Neurosci 29(50):15745–15755

    CAS  Google Scholar 

  • Morris MJ, Dausse JP, Devynck MA, Meyer P (1980) Ontogeny of a1 and a2-adrenoceptors in rat brain. Brain Res 190:268–271

    CAS  Google Scholar 

  • Murrin LC, Sanders JD, Bylund DB (2007) Comparison of the maturation of the adrenergic and serotonergic neurotransmitter systems in the brain: implications for differential drug effects on juveniles and adults. Biochem Pharmacol 73:1225–1236

    CAS  Google Scholar 

  • Nalepa I, Kreiner G, Kowalska M, Sanak M, Zelek-Molik A, Vetulani J (2002) Repeated imipramine and electroconvulsive shock increase alpha 1A-adrenoceptor mRNA level in rat prefrontal cortex. Eur J Pharmacol 444:151–159

    CAS  Google Scholar 

  • Nalepa I, Kreiner G, Bielawski A, Rafa-Zabłocka K, Roman A (2013) α1-Adrenergic receptor subtypes in the central nervous system: insights from genetically engineered mouse models. Pharmacol Rep 65:1489–1497

    CAS  Google Scholar 

  • Oakley RH, Laporte SA, Holt JA, Caron MG, Barak LS (2000) Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J Biol Chem 275:17201–17210

    CAS  Google Scholar 

  • Oakley RH, Laporte SA, Holt JA, Barak LS, Caron MG (2001) Molecular determinants underlying the formation of stable intracellular G protein-coupled receptor-beta-arrestin complexes after receptor endocytosis. J Biol Chem 276:19452–19460

    CAS  Google Scholar 

  • Papay R, Gaivin R, Jha A, McCune DF, McGrath JC, Rodrigo MC, Simpson PC, Doze VA, Perez DM (2006) Localization of the mouse alpha1A-adrenergic receptor (AR) in the brain: alpha1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors. J Comp Neurol 497(2):209–222

    CAS  Google Scholar 

  • Pare WP (1994) Open field, learned helplessness, conditioned defensive burying, and forced-swim tests in WKY rats. Physiol Behav 55:433

    CAS  Google Scholar 

  • Peskind ER, Bonner LT, Hoff DJ, Raskind MA (2003) Prazosin reduceds trauma-related nightmares in older men with chronic posttraumatic stress disorder. J Geriatr Psychiatry Neurol 16:165–171

    Google Scholar 

  • Peters DA (1984) Prenatal stress: effect on development of rat brain adrenergic receptors. Pharmacol Biochem Behav 21:417–422

    CAS  Google Scholar 

  • Philipp M, Hein L (2004) Adrenergic receptor knockout mice: distinct functions of 9 receptor subtypes. Pharmacol Ther 101(1):65–74

    CAS  Google Scholar 

  • Piascik MT, Perez DM (2001) Alpha1-adrenergic receptors: new insights and directions. J Pharmacol Exp Ther 298(2):403–410

    CAS  Google Scholar 

  • Pradhan AA, Perroy J, Walwyn WM, Smith ML, Vicente-Sanchez A, Segura L, Bana A, Kieffer BL, Evans CJ (2016) Agonist-specific recruitment of arrestin isoforms differentially modify delta opioid receptor function. J Neurosci 36:3541–3551

    CAS  Google Scholar 

  • Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463:3–33

    CAS  Google Scholar 

  • Qiong W, Man L, Wei D, Feng S, Weiwen W (2015) The different effects of maternal separation on spatial learning and reversal learning in rats. Behav Brain Res 280:16–23

    Google Scholar 

  • Raineki C, Moriceau S, Sullivan RM (2010) Developing a neurobehavioral animal model of infant attachment to an abusive caregiver. Biol Psychiatry 67:1137–1145

    Google Scholar 

  • Rao U, Chen LA, Bidesi AS, Shad MU, Thomas MA, Hammen CL (2010) Hippocampal changes associated with early-life adversity and vulnerability to depression. Biol Psychiatry 67:357–364

    Google Scholar 

  • Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Tröster K, Thomas RG, McFall MM (2003) Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry 160:371–373

    Google Scholar 

  • Rebec GV, Grabner CP, Johnson M, Pierce RC, Bardo MT (1997) Transient increases in catecholaminergic activity in medial prefrontal cortex and nucleus accumbens shell during novelty. Neuroscience 76:707–714

    CAS  Google Scholar 

  • Rehavi M, Ramot O, Yavetz B, Sokolovsky M (1980) Amitriptyline: long-term treatment elevates alpha-adrenergic and muscarinic receptor binding in mouse brain. Brain Res 194(2):443–453

    CAS  Google Scholar 

  • Ressler KJ, Nemeroff CB (2000) Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety 12:2–19

    Google Scholar 

  • Rincel M, Lépinay AL, Janthakhin Y, Soudain G, Yvon S, Da Silva S, Joffre C, Aubert A, Séré A, Layé S, Theodorou V, Ferreira G, Darnaudéry M (2018) Maternal high-fat diet and early life stress differentially modulate spine density and dendritic morphology in the medial prefrontal cortex of juvenile and adult rats. Brain Struct Funct 223:883–895

    CAS  Google Scholar 

  • Robins MT, Chiang T, Berry JN, Ko MJ, Ha JE, van Rijn RM (2018) Behavioral characterization of β-arrestin 1 knockout mice in anxiety-like and alcohol behaviors. Front Behav Neurosci 12:54

    Google Scholar 

  • Saitoh A, Kimura Y, Suzuki T, Kawai K, Nagase H, Kamei J (2004) Potential anxiolytic and antidepressant-like activities of SNC80, a selective delta-opioid agonist, in behavioral models in rodents. J Pharmacol Sci 95:374–380

    CAS  Google Scholar 

  • Saitoh A, Suzuki S, Soda A, Ohashi M, Yamada M, Oka JI, Nagase H, Yamada M (2018) The delta opioid receptor agonist KNT-127 in the prelimbic medial prefrontal cortex attenuates veratrine-induced anxiety-like behaviors in mice. Behav Brain Res 336:77–84

    CAS  Google Scholar 

  • Sanders J, Happe H, Bylund D, Murrin LC (2011) Changes in postnatal norepinephrine alter alpha-2 adrenergic receptor development. Neuroscience 192:761–772

    CAS  Google Scholar 

  • Sara SJ, Dyon-laurent C, Herd A (1995) Novelty seeking behavior in the rat is dependent upon the integrity of the noradrenergic system. Cogn Brain Res 2:181–187

    CAS  Google Scholar 

  • Seibenhener ML, Wooten MC (2015) Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J Vis Exp 96:e52434

    Google Scholar 

  • Sestakova N, Puzserova A, Kluknavsky M, Bernatova I (2013) Determination of motor activity and anxiety-related behaviour in rodents: methodological aspects and role of nitric oxide. Interdiscip Toxicol 6:126–135

    Google Scholar 

  • Sevelinges Y, Moriceau S, Holman P, Miner C, Muzny K, Gervais R, Mouly AM, Sullivan RM (2007) Enduring effects of infant memories: infant odor-shock conditioning attenuates amygdala activity and adult fear conditioning. Biol Psychiatry 62:1070–1079

    Google Scholar 

  • Sevelinges Y, Mouly MA, Moriceau S, Raineki C, Forest C, Sullivan RM (2011) Adult depression-like behavior and amygdala dysfunction rescued by odor previously paired with shock in infancy. Dev Cogn Neurosci 1:77–87

    Google Scholar 

  • Snoddy AM, Tessel RE (1985) Prazosin: effect on psychomotor-stimulant cues and locomotor activity in mice. Eur J Pharmacol 116:221–228

    CAS  Google Scholar 

  • Soares-Cunha C, Coimbra B, Borges S, Domingues AV, Silva D, Sousa N, Rodrigues AJ (2018) Mild prenatal stress causes emotional and brain structural modifications in rats of both sexes. Front Behav Neurosci 12:129

    Google Scholar 

  • Stone EA, Zhang Y, Rosengarten H, Yeretsian J, Quartermain D (1999) Brain alpha 1-adrenergic neurotransmission is necessary for behavioral activation to environmental change in mice. Neuroscience 94:1245–1252

    CAS  Google Scholar 

  • Stone EA, Yan LIN, Ahsan MR, Lehmann ML, Yeretsian J, Quartermain D (2006) Role of CNS alpha-1-adrenoceptor activity in central fos responses to novelty. Synapse 59:299–307

    CAS  Google Scholar 

  • Stone EA, Lin Y, Sarfraz Y, Quartermain D (2011) The role of the central noradrenergic system in behavioral inhibition. Brain Res Rev 67:193–208

    CAS  Google Scholar 

  • Sullivan GM, Coplan JD, Kent JM, Gorman JM (1999) The noradrenergic system in pathological anxiety: a focus on panic with relevance to generalized anxiety and phobias. Biol Psychiatry 46:1205–1218

    CAS  Google Scholar 

  • Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP, Kim DM (2003) The neurobiological consequences of early stress and childhood maltreatment. Neurosci Biobehav Rev 27:33–44

    Google Scholar 

  • Teicher MH, Tomoda A, Andersen SL (2006) Neurobiological consequences of early stress and childhood maltreatment: are results from human and animal studies comparable? Ann N Y Acad Sci 1071:313–323

    Google Scholar 

  • Teicher MH, Anderson CM, Polcari A (2012) Childhood maltreatment is associated with reduced volume in the hippocampal subfields CA3, dentate gyrus, and subiculum. Proc Natl Acad Sci U S A 109:E563–E572

    CAS  Google Scholar 

  • Tian X, Kang DS, Benovic JL (2014) β-arrestins and G protein-coupled receptor trafficking. Handb Exp Pharmacol 219:173–186

    CAS  Google Scholar 

  • Uberti M, Hall RA, Minneman KP (2003) Subtype-specific dimerization of alpha 1adrenoceptors: effects on receptor expression and pharmacological properties. Mol Pharmacol 64:1379–1390

    CAS  Google Scholar 

  • Vaiserman AM (2015) Epigenetic programming by early-life stress: evidence from human populations. Dev Dyn 244:254–265

    CAS  Google Scholar 

  • van Harmelen AL, de Jong PJ, Glashouwer KA, Spinhoven P, Penninx BW, Elzinga BM (2010) Child abuse and negative explicit and automatic self-associations: the cognitive scars of emotional maltreatment. Behav Res Ther 48:486–494

    Google Scholar 

  • van Rijn RM, Brissett DI, Whistler JL (2010) Dual efficacy of delta opioid receptor-selective ligands for ethanol drinking and anxiety. J Pharmacol Exp Ther 335:133–139

    Google Scholar 

  • Varese F, Smeets F, Drukker M, Lieverse R, Lataster T, Viechtbauer W, Read J, van Os J, Bentall RP (2012) Childhood adversities increase the risk of psychosis: a meta-analysis of patient-control, prospective- and cross-sectional cohort studies. Schizophr Bull 38:661–671

    Google Scholar 

  • Velley L, Kempf E, Cardo B (1982) Locomotor activity of rats after stimulation of then nucleus locus coeruleus region or after lesion of the dorsal noradrenergic bundle: effects of clonidine, prazosin and yohimbine. Psychopharmacology 78:239–244

    CAS  Google Scholar 

  • Vicente-Sanchez A, Dripps IJ, Tipton AF, Akbari H, Akbari A, Jutkiewicz EM, Pradhan AA (2018) Tolerance to high-internalizing delta opioid receptor agonist is critically mediated by arrestin 2. Br J Pharmacol 175:3050–3059

    CAS  Google Scholar 

  • Vindas MA, Fokos S, Pavlidis M, Höglund E, Dionysopoulou S, Ebbesson LOE, Papandroulakis N, Dermon CR (2018) Early life stress induces long-term changes in limbic areas of a teleost fish: the role of catecholamine systems in stress coping. Sci Rep 8:5638

    Google Scholar 

  • Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, Brummer M, Staib L, Vermetten E, Charney DS, Nemeroff CB, Bremner JD (2002) Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry 159:2072–2080

    Google Scholar 

  • Zohar J, Westenberg HG (2000) Anxiety disorders: a review of tricyclic antidepressants and selective serotonin reuptake inhibitors. Acta Psychiatr Scand Suppl 403:39–49

    CAS  Google Scholar 

  • Zurkovsky L, Sedaghat K, Ahmed MR, Gurevich VV, Gurevich EV (2017) Arrestin-2 and arrestin-3 differentially modulate locomotor responses and sensitization to amphetamine. Neuropharmacology 121:20–29

    CAS  Google Scholar 

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Acknowledgements

This work was supported by a grant from Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences.

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  1. Mohammad Amini and Leila Derafshpour contributed equally to this work.

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  1. Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

    Maryam Mahmoodkhani, Mohammad Amini, Leila Derafshpour & Nasrin Mehranfard

  2. Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Maedeh Ghasemi

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Mahmoodkhani, M., Amini, M., Derafshpour, L. et al. Negative relationship between brain α1A-AR neurotransmission and βArr2 levels in anxious adolescent rats subjected to early life stress. Exp Brain Res 238, 2833–2844 (2020). https://doi.org/10.1007/s00221-020-05937-1

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