GABA_A receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: Possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders

References

• Agis Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A. Characterization of neurons that express enzymes mediating neurosteroid biosynthesis. Proc Natl Acad Sci USA 2006; 103: 14602–14607
   PubMed Web of Science ®Google Scholar
• Akbarian S, Huntsman MM, Kim JJ, Tafazzoli A, Potkin SG, Bunney WEJ, Jones EG. GABAA receptor subunit gene expression in human prefrontal cortex: Comparison of schizophrenics and controls. Cereb Cortex 1995; 5: 550–560
   PubMed Web of Science ®Google Scholar
• Banerjee PK, Tillakaratne NJ, Brailowsky S, Olsen RW, Tobin AJ, Snead OC, 3rd. Alterations in GABAA receptor alpha 1 and alpha 4 subunit mRNA levels in thalamic relay nuclei following absence-like seizures in rats. Exp Neurol 1998; 154: 213–223
   PubMed Web of Science ®Google Scholar
• Belelli D, Lambert JJ. Neurosteroids: Endogenous regulators of the GABAA receptor. Nat Rev Neurosci 2005; 6: 565–575
   PubMed Web of Science ®Google Scholar
• Cagetti E, Liang J, Spigelman I, Olsen R. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol 2003; 63: 53–64
   PubMed Web of Science ®Google Scholar
• Caldji C, Diorio J, Anisman H, Meaney M. Maternal behavior regulates benzodiazepine/GABAA receptor subunit expression in brain regions associated with fear in BALB/c and C57BL/6 mice. Neuropsychopharmacology 2004; 29: 1344–1352
   PubMed Web of Science ®Google Scholar
• Cheney DL, Uzunov DP, Guidotti A, Costa E. Gas chromatographic-mass fragmentographic quantitation of 3 alpha-hydroxy-5 alpha-pregnan-20-one (allopregnanolone) and its precursors in blood and brain of adrenalectomized and castrated rats. J Neurosci 1995; 15: 4641–4650
   PubMed Web of Science ®Google Scholar
• Costa E, Guidotti A. Benzodiazepines on trial: A research strategy for their rehabilitation. Trends Pharmacol Sci 1996; 17: 192–200
   PubMed Web of Science ®Google Scholar
• Costa E, Auta J, Grayson DR, Matsumoto K, Pappas GD, Zhang X, Guidotti A. GABAA receptors and benzodiazepines: A role for dendritic resident subunit mRNAs. Neuropharmacology 2002; 43: 925–937
   PubMed Web of Science ®Google Scholar
• Crestani F, Martin JR, Mohler H, Rudolph U. Mechanism of acton of the hypnotic zolpidem in vivo. Br J Pharmacol 2000; 131: 1251–1254
   PubMed Web of Science ®Google Scholar
• Dean B, Hussain T, Hayes W, Scarr E, Kitsoulis S, Hill C, Opeskin K, Copolov DL. Changes in serotonin2A and GABAA receptors in schizophrenia: Studies on the human dorsolateral prefrontal cortex. J Neurochem 1999; 72: 1593–1599
   PubMed Web of Science ®Google Scholar
• Dong E, Matsumoto K, Tohda M, Kaneko Y, Watanabe H. Diazepam binding inhibitor (DBI) gene expression in the brains of socially isolated and group-housed mice. Neurosci Res 1999; 33: 171–177
   PubMed Web of Science ®Google Scholar
• Dong E, Matsumoto K, Uzunova V, Sugaya I, Takahata H, Nomura H, Watanabe H, Costa E, Guidotti A. Brain 5α-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation. Proc Natl Acad Sci USA 2001; 98: 2849–2854
   PubMed Web of Science ®Google Scholar
• Dubrovsky BO. Steroids, neuroactive steroids and neurosteroids in psychopathology. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29: 169–192
   PubMed Web of Science ®Google Scholar
• Eser D, Romeo E, Baghai TC, di Michele F, Schule C, Pasini A, Zwanzger P, Padberg F, Rupprecht R. Neuroactive steroids as modulators of depression and anxiety. Neuroscience 2006; 138: 1041–1048
   PubMed Web of Science ®Google Scholar
• Frye CA, Rhodes ME, Petralia SM, Walf AA, Sumida K, Edinger KL. 3α-Hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors. Neuroscience 2006; 138: 1007–1014
   PubMed Web of Science ®Google Scholar
• Gentsch JM, Lichtsteiner M, Frischknecht HR, Feer H, Siegfried B. Isolation-induced locomotor hyperactivity and hypoalgesia in rats are prevented by handling and recovered by resocialization. Physiol Behav 1988; 43: 13–16
   PubMed Web of Science ®Google Scholar
• Girdler SS, Straneva PA, Light KC, Pedersen CA, Morrow AL. Allopregnanolone levels and reactivity to mental stress in premenstrual dysphoric disorder. Biol Psychiatry 2001; 49: 788–797
   PubMed Web of Science ®Google Scholar
• Griffin LD, Mellon SH. Selective serotonin reuptake inhibitors directly alter activity of neurosteroidogenic enzymes. Proc Natl Acad Sci USA 1999; 96: 13512–13517
   PubMed Web of Science ®Google Scholar
• Guidotti A, Costa E. Can the antidysphoric and anxiolytic profiles of selective serotonin reuptake inhibitors be related to their ability to increase brain 3α 5α-tetrahydroprogesterone (allopregnanolone) availability?. Biol Psychiatry 1998; 44: 865–873
   PubMed Web of Science ®Google Scholar
• Guidotti A, Dong E, Matsumoto K, Pinna G, Rasmusson AM, Costa E. The socially-isolated mouse: A model to study the putative role of allopregnanolone and 5α-dihydroprogesterone in psychiatric disorders. Brain Res Brain Res Rev 2001; 37: 110–115
   PubMed Web of Science ®Google Scholar
• Guidotti A, Auta J, Davis JM, Dong E, Grayson DR, Veldic M, Zhang X, Costa E. GABAergic dysfunction in schizophrenia: New treatment strategies on the horizon. Psychopharmacology (Berl) 2005; 180: 191–205
   PubMed Web of Science ®Google Scholar
• Hall FS. Social deprivation of neonatal, adolescent, and adult rats has distinct neurochemical and behavioral consequences. Crit Rev Neurobiol 1998; 12: 129–162
   PubMed Web of Science ®Google Scholar
• Hatch AM, Balazs T, Wiberg GS, Grice HC. Long-term isolation in rats. Science 1963; 142: 507–508
   PubMed Web of Science ®Google Scholar
• Heidbreder CA, Weiss IC, Domeney AM, Pryce C, Homberg J, Hedou G, Feldon J, Moran MC, Nelson P. Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome. Neuroscience 2000; 100: 749–768
   PubMed Web of Science ®Google Scholar
• Hilakivi LA, Ota M, Lister RG. Effect of isolation on brain monoamines and the behavior of mice in tests of exploration, locomotion, anxiety and behavioral ’despair’. Pharmacol Biochem Behav 1989; 33: 371–374
   PubMed Web of Science ®Google Scholar
• Hodge GK, Butcher LL. Catecholamine correlates of isolation-induced aggression in mice. Eur J Pharmacol 1975; 31: 81–93
   PubMed Web of Science ®Google Scholar
• Impagnatiello F, Pesold C, Longone P, Caruncho H, Fritschy JM, Costa E, Guidotti A. Modifications of γ-aminobutyric acidA receptor subunit expression in rat neocortex during tolerance to diazepam. Mol Pharmacol 1996; 49: 822–831
   PubMed Web of Science ®Google Scholar
• Ishikawa M, Mizukami K, Iwakiri M, Hidaka S, Asada T. GABAA receptor γ subunits in the prefrontal cortex of patients with schizophrenia and bipolar disorder. Neuroreport 2004; 15: 1809–1812
   PubMed Web of Science ®Google Scholar
• Jones GH, Marsden CA, Robbins TW. Behavioral rigidity and rule-learning deficits following isolation-rearing in the rat: Neurochemical correlates. Behav Brain Res 1991; 43: 35–50
   PubMed Web of Science ®Google Scholar
• Kendell SF, Krystal JH, Sanacora G. GABA and glutamate systems as therapeutic targest in depression and mood disorders. Expert Opin Ther Targets 2005; 9: 153–168
   PubMed Web of Science ®Google Scholar
• Kim JW, Kirkpatrick B. Social isolation in animal models of relevance to neuropsychiatric disorders. Biol Psychiatry 1996; 40: 918–922
   PubMed Web of Science ®Google Scholar
• Krystall JH, Sanacora G, Bumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF. Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Mol Psychiatry 2002; 7: S71–S80
   Web of Science ®Google Scholar
• Kumar S, Fleming RL, Morrow AL. Ethanol regulation of γ-aminobutyric acidA receptors: Genomic and nongenomic mechanisms. Pharmacol Ther 2004; 101: 211–226
   PubMed Web of Science ®Google Scholar
• Lambert JJ, Belelli D, Peden DR, V AW, Peters JA. Neurosteroid modulation of GABAA receptors. Prog Neurobiol 2003; 71: 67–80
   PubMed Web of Science ®Google Scholar
• Lewis DA. GABAergic local circuit neurons and prefrontal cortical dysfunction in schizophrenia. Brain Res Brain Res Rev 2000; 31: 270–276
   PubMedGoogle Scholar
• Marx CE, Stevens RD, Shampine LJ, Uzunova V, Trost WT, Butterfield MI, Massing MW, Hamer RM, Morrow AL, Lieberman JA. Neuroactive steroids are altered in schizophrenia and bipolar disorder: Relevance to pathophysiology and therapeutics. Neuropsychopharmacology 2006; 31: 1249–1263
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Cai B, Satoh T, Ohta H, Watanabe H. Desipramine enhances isolation-induced aggressive behavior in mice. Pharmacol Biochem Behav 1991; 39: 167–170
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Ojima K, Watanabe H. Noradrenergic denervation attenuates desipramine enhancement of aggressive behavior in isolated mice. Pharmacol Biochem Behav 1995; 50: 481–484
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Ojima K, Watanabe H. Neurosteroidal modulation of social-isolation stress-induced decrease in pentobarbital sleep in mice. Brain Res 1996; 708: 1–6
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Ojima K, Watanabe H. Central corticotropin-releasing factor and benzodiazepine receptor systems are involved in the social isolation stress-induced decrease in ethanol sleep in mice. Brain Res 1997; 753: 318–321
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Uzunova V, Pinna G, Taki K, Uzunov DP, Watanabe H, Mienville JM, Guidotti A, Costa E. Permissive role of brain allopregnanolone content in the regulation of pentobarbital-induced righting reflex loss. Neuropharmacology 1999; 38: 955–963
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Nomura H, Murakami Y, Taki K, Takahata H, Watanabe H. Long-term social isolation enhances picrotoxin seizure susceptibility in mice: Upregulatory role of endogenous brain allopregnanolone in GABAergic systems. Pharmacol Biochem Behav 2003; 75: 831–835
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Pinna G, Puia G, Guidotti A, Costa E. Social isolation stress-induced aggression in mice: A model to study the pharmacology of neurosteroidogenesis. Stress 2005; 8: 85–93
   PubMed Web of Science ®Google Scholar
• Miczek KA, Fish EW, De Bold JF. Neurosteroids, GABAA receptors, and escalated aggressive behavior. Horm Behav 2003; 44: 242–257
   PubMed Web of Science ®Google Scholar
• Ojima K, Matsumoto K, Tohda M, Watanabe H. Hyperactivity of central noradrenergic and CRF systems is involved in social isolation-induced decrease in pentobarbital sleep. Brain Res 1995; 684: 87–94
   PubMed Web of Science ®Google Scholar
• Ojima K, Matsumoto K, Watanabe H. Flumazenil reverses the decrease in the hypnotic activity of pentobarbital by social isolation stress: Are endogenous benzodiazepine receptor ligands involved?. Brain Res 1997; 745: 127–133
   PubMed Web of Science ®Google Scholar
• Orchinik M, Weiland NG, McEwen B. Chronic exposure to stress levels of corticosterone alters GABAA receptor subunit mRNA levels in rat hippocampus. Brain Res Mol Brain Res 1995; 34: 29–37
   PubMedGoogle Scholar
• Orchinik M, Carroll SS, Li YH, McEwen BS, Weiland NG. Heterogeneity of hippocampal GABAA receptors: Regulation by corticosterone. J Neurosci 2001; 21: 330–339
   PubMed Web of Science ®Google Scholar
• Pashko S, DeTurck KH, Vogel WH. Use of the catheterized rat in studies on social interactions and plasma catecholamines. Pharmacol Biochem Behav 1980; 13: 471–473
   PubMed Web of Science ®Google Scholar
• Pinna G, Uzunova V, Matsumoto K, Puia G, Mienville J-M, Costa E, Guidotti A. Brain allopregnanolone regulates the potency of the GABAA receptor agonist muscimol. Neuropharmacology 2000; 39: 440–448
   PubMed Web of Science ®Google Scholar
• Pinna G, Dong E, Matsumoto K, Costa E, Guidotti A. In socially isolated mice, the reversal of brain allopregnanolone down-regulation mediates the anti-aggressive action of fluoxetine. Proc Natl Acad Sci USA 2003; 100: 2035–2040
   PubMed Web of Science ®Google Scholar
• Pinna G, Costa E, Guidotti A. Fluoxetine and norfluoxetine stereospecifically facilitate pentobarbital sedation by increasing neurosteroids. Proc Natl Acad Sci USA 2004; 101: 6222–6225
   PubMed Web of Science ®Google Scholar
• Pinna G, Costa E, Guidotti A. Changes in brain testosterone and allopregnanolone biosynthesis elicit aggressive behavior. Proc Natl Acad Sci USA 2005; 102: 2135–2140
   PubMed Web of Science ®Google Scholar
• Pinna G, Agis-Balboa RC, Zhubi A, Matsumoto K, Grayson DR, Costa E, Guidotti A. Imidazenil and diazepam increase locomotor activity in mice exposed to protracted social isolation. Proc Natl Acad Sci USA 2006a; 103: 4275–4280
   PubMed Web of Science ®Google Scholar
• Pinna G, Costa E, Guidotti A. Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake. Psychopharmacology 2006b; 186: 362–372
   PubMed Web of Science ®Google Scholar
• Pisu MG, Serra M. Neurosteroids and neuroactive drugs in mental disorders. Life Sci 2004; 74: 3181–3197
   PubMed Web of Science ®Google Scholar
• Puia G, Santi MR, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg PH, Costa E. Neurosteroids act on recombinant human GABAA receptors. Neuron 1990; 4: 759–765
   PubMed Web of Science ®Google Scholar
• Puia G, Vicini S, Seeburg PH, Costa E. Influence of recombinant gamma-aminobutyric acid—a receptor subunit composition on the action of allosteric modulators of gamma-aminobutyric acid-gated Cl− current. Mol Pharmacol 1991; 39: 691–696
   PubMed Web of Science ®Google Scholar
• Puia G, Ducic I, Vicini S, Costa E. Does neurosteroid modulatory efficacy depend on GABAA receptor subunit composition?. Receptors Channels 1993; 1: 135–142
   PubMedGoogle Scholar
• Puia G, Mienville J-M, Matsumoto K, Takahata H, Watanabe H, Costa E, Guidotti A. On the putative physiological role of allopregnanolone on GABAA receptor function. Neuropharmacology 2003; 44: 49–55
   PubMed Web of Science ®Google Scholar
• Rasmusson AM, Pinna G, Paliwal P, Weisman D, Gottschalk C, Charney D, Krystal J, Guidotti A. Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder. Biol Psychiatry 2006; 60: 704–713
   PubMed Web of Science ®Google Scholar
• Romeo E, Strohle A, Spalletta G, diMichele F, Hermann B, Holsboer F, Pasini A, Rupprecht R. Effects of antidepressant treatment on neuroactive steroids in major depression. Am J Psychiatry 1998; 155: 910–913
   PubMed Web of Science ®Google Scholar
• Rudolph R, Mohler H. Analysis of GABAA receptor function and dissection of the pharmacology of benzodiazepines and general anesthetics through mouse genetics. Annu Rev Pharmacol Toxicol 2004; 44: 475–498
   PubMed Web of Science ®Google Scholar
• Rudolph U, Crestani F, Benke D, Brunig I, Benson JA, Fritschy JM, Martin JR, Bluethmann H, Mohler H. Benzodiazepine actions mediated by specific γ-aminobutyric acidA receptor subtypes. Nature 1999; 401: 796–800
   PubMed Web of Science ®Google Scholar
• Schule C, di Michele F, Baghai T, Romeo E, Bernardi G, Zwanzger P, Padberg F, Pasini A, Rupprecht R. Influence of sleep deprivation on neuroactive steroids in major depression. Neuropsychopharmacology 2003; 28: 577–581
   PubMed Web of Science ®Google Scholar
• Semeniuk T, Jhangri GS, Le Melledo JM. Neuroactive steroid levels in patients with generalized anxiety disorder. J Neuropsychiatry Clin Neurosci 2001; 13: 396–398
   PubMed Web of Science ®Google Scholar
• Serra M, Pisu MG, Littera M, Papi G, Sanna E, Tuveri F, Usala L, Purdy RH, Biggio G. Social isolation-induced decreases in both the abundance of neuroactive steroids and GABAA receptor function in rat brain. J Neurochem 2000; 75: 732–740
   PubMed Web of Science ®Google Scholar
• Serra M, Sanna E, Mostallino MC, Biggio G. Social isolation stress and neuroactive steroids. Eur Neuropsychopharmacol 2007; 17: 1–11
   PubMed Web of Science ®Google Scholar
• Smith SS, Gong QH, Hsu FC, Markowitz RS, ffrench-Mullen JM, Li X. GABAA receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature 1998a; 392: 926–930
   PubMed Web of Science ®Google Scholar
• Smith SS, Gong QH, Li X, Moran MH, Bitran D, Frye CA, Hsu FC. Withdrawal from 3α-OH-5α-pregnan-20-One using a pseudopregnancy model alters the kinetics of hippocampal GABAA-gated current and increases the GABAA receptor α4 subunit in association with increased anxiety. J Neurosci 1998b; 18: 5275–5284
   PubMed Web of Science ®Google Scholar
• Stroehle A, Romeo E, Hermann B, Pasini A, Spalletta G, di Michele F, Holsboer F, Rupprecht R. Concentrations of 3α-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery. Biol Psychiatry 1999; 45: 274–277
   PubMed Web of Science ®Google Scholar
• Stroehle A, Pasini A, Romeo E, Hermann B, Spalletta G, di Michele F, Holsboer F, Rupprecht R. Fluoxetine decreases concentrations of 3α, 5α-tetrahydrodeoxycorticosterone (THDOC) in major depression. J Psychiatr Res 2000; 34: 183–186
   PubMed Web of Science ®Google Scholar
• Trauger JW, Jiang A, Stearns BA, LoGrasso PV. Kinetics of allopregnanolone formation catalyzed by human 3α-hydroxysteriod dehydrogenase type III (AKR1C2). Biochemistry 2002; 41: 13451–13459
   PubMed Web of Science ®Google Scholar
• Uzunov DP, Cooper TB, Costa E, Guidotti A. Fluoxetine-elicited changes in brain neurosteroid content measured by negative ion mass fragmentography. Proc Natl Acad Sci USA 1996; 93: 12599–12604
   PubMed Web of Science ®Google Scholar
• Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A. Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar depression who are receiving fluoxetine or fluvoxamine. Proc Natl Acad Sci USA 1998; 95: 3239–3244
   PubMed Web of Science ®Google Scholar
• Uzunova V, Wrynn AS, Kinnunen A, Ceci M, Kohler C, Uzunov DP. Chronic antidepressants reverse cerebrocortical allopregnanolone decline in the olfactory-bulbectomized rat. Eur J Pharmacol 2004; 486: 31–34
   PubMed Web of Science ®Google Scholar
• Uzunova V, Sampson L, Uzunov DP. Relevance of endogenous 3alpha-reduced neurosteroids to depression and antidepressant action. Psychopharmacology (Berl) 2006; 186: 351–361
   PubMed Web of Science ®Google Scholar
• Valzelli L. The “Isolation Syndrome” in mice. Psychopharmacologia (Berl) 1973; 31: 305–320
   PubMed Web of Science ®Google Scholar
• Valzelli L. Psychopharmacology of aggression: An overview. Int Pharmacopsychiatry 1981; 16: 39–48
   PubMedGoogle Scholar
• van Broekhoven F, Verkes RJ. Neurosteroids in depression: A review. Psychopharmacology (Berl) 2003; 165: 97–110
   PubMed Web of Science ®Google Scholar
• Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ. Functional characterization of human γ-aminobutyric acidA receptors containing the α4 subunit. Mol Pharmacol 1996; 50: 670–678
   PubMed Web of Science ®Google Scholar
• Weiss IC, Domeney AM, Heidbreder CA, Moreau JL, Feldon J. Early social isolation, but not maternal separation, affects behavioral sensitization to amphetamine in male and female adult rats. Pharmacol Biochem Behav 2001; 70: 397–409
   PubMed Web of Science ®Google Scholar
• Wong DT, Bymaster FP, Reid LR, Mayle DA, Krushinski JH, Robertson DW. Norfluoxetine enantiomers as inhibitors of serotonin uptake in rat brain. Neuropsychopharmacology 1993; 8: 337–344
   PubMed Web of Science ®Google Scholar