Inhibition of 5α-reductase in the nucleus accumbens counters sensorimotor gating deficits induced by dopaminergic activation

Psychoneuroendocrinology

Volumn 37, Issue 10, 2012, Pages 1630-1645

  Devoto, Paola ^a   Frau, Roberto ^a   Bini, Valentina ^a   Pillolla, Giuliano ^a   Saba, Pierluigi ^a   Flore, Giovanna ^a   Corona, Marta ^a   Marrosu, Francesco ^a   Bortolato, Marco ^a,b  

^a UNIVERSITY OF CAGLIARI   (Italy)

^b UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

5 reductase; Dopamine; Finasteride; Nucleus accumbens; Prepulse inhibition; Schizophrenia; Sensorimotor gating

Indexed keywords

AMPHETAMINE; APOMORPHINE; DOPAMINE; DOPAMINE RECEPTOR; FINASTERIDE; STEROID 5ALPHA REDUCTASE;

ACOUSTIC STARTLE REFLEX; AMYGDALOID NUCLEUS; ANIMAL EXPERIMENT; ARTICLE; BRAIN REGION; CONTROLLED STUDY; DOPAMINERGIC ACTIVITY; DOPAMINERGIC TRANSMISSION; DRUG RESPONSE; ENZYME INHIBITION; HIPPOCAMPUS; MALE; MEDIAL PREFRONTAL CORTEX; MENTAL DISEASE; MICRODIALYSIS; NEUROPSYCHIATRIC DISORDER; NONHUMAN; NUCLEUS ACCUMBENS; ORCHIECTOMY; PREPULSE INHIBITION; PRIORITY JOURNAL; RAT; SCHIZOPHRENIA; SENSORIMOTOR GATING DEFICIT; SENSORIMOTOR NEUROPATHY; STARTLE REFLEX; VENTRAL HIPPOCAMPUS;

5-ALPHA REDUCTASE INHIBITORS; ANIMALS; APOMORPHINE; CHOLESTENONE 5 ALPHA-REDUCTASE; DEXTROAMPHETAMINE; DOPAMINE AGENTS; FINASTERIDE; MALE; NUCLEUS ACCUMBENS; ORCHIECTOMY; RATS; RATS, SPRAGUE-DAWLEY; SENSORY GATING; STARTLE REACTION;

EID: 84865566076     PISSN: 03064530     EISSN: 18733360     Source Type: Journal    
DOI: 10.1016/j.psyneuen.2011.09.018     Document Type: Article

References (94)

1. Agís-Balboa R.C., Pinna G., Zhubi A., Maloku E., Veldic M., Costa E., Guidotti A. Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:14602-14607.
2. Andreasen N.C., Swayze V.W., Flaum M., Yates W.R., Arndt S., McChesney C. Ventricular enlargement in schizophrenia evaluated with computed tomographic scanning. Effects of gender, age, and stage of illness. Arch. Gen. Psychiatry 1990, 47:1008-1015.
3. Barbaccia M.L., Roscetti G., Trabucchi M., Purdy R.H., Mostallino M.C., Concas A., Biggio G. The effects of inhibitors of GABAergic transmission and stress on brain and plasma allopregnanolone concentrations. Br. J. Pharmacol. 1997, 120:1582-1588.
4. Barbaccia M.L., Affricano D., Purdy R.H., Maciocco E., Spiga F., Biggio G. Clozapine, but not haloperidol, increases brain concentrations of neuroactive steroids in the rat. Neuropsychopharmacology 2001, 25:489-497.
5. Beatty W.W., Dodge A.M., Traylor K.L. Stereotyped behavior elicited by amphetamine in the rat: influences of the testes. Pharmacol. Biochem. Behav. 1982, 16:565-568.
6. Bitar M.S., Ota M., Linnoila M., Shapiro B.H. Modification of gonadectomy-induced increases in brain monoamine metabolism by steroid hormones in male and female rats. Psychoneuroendocrinology 1991, 16:547-557.
7. Bortolato M., Frau R., Aru G.N., Orru' M., Gessa G.L. Baclofen reverses the reduction in prepulse inhibition of the acoustic startle response induced by dizocilpine, but not by apomorphine. Psychopharmacology 2004, 171:322-330.
8. Bortolato M., Muroni A., Marrosu F. Treatment of Tourette's syndrome with finasteride. Am. J. Psychiatry 2007, 164:1914-1915.
9. Bortolato M., Frau R., Orru' M., Bourov Y., Marrosu F., Mereu G., Devoto P., Gessa G.L. Antipsychotic-like properties of 5-alpha-reductase inhibitors. Neuropsychopharmacology 2008, 33:3146-3156.
10. Bortolato, M., Cannas, A., Solla, P., Bini, V., Puligheddu, M., Marrosu, F. Finasteride attenuates pathological gambling in Parkinson's disease patients. J. Clin. Psychopharmacol., in press.
11. Bortolato M., Devoto P., Roncada P., Frau R., Flore G., Saba P., Pistritto G., Soggiu A., Pisanu S., Zappala' A., Ristaldi M.S., Tattoli M., Cuomo V., Marrosu F., Barbaccia M.L. Isolation rearing-induced reduction of brain 5α-reductase expression: relevance to dopaminergic impairments. Neuropharmacology 2011, 60:1301-1308.
12. Braff D.L., Grillon C., Geyer M.A. Gating and habituation of the startle reflex in schizophrenic patients. Arch. Gen. Psychiatry 1992, 49:206-215.
13. Braff D.L., Geyer M.A., Light G.A., Sprock J., Perry W., Cadenhead K.S., Swerdlow N.R. Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia. Schizophr. Res. 2001, 49:171-178.
14. Braff D.L., Geyer M.A., Swerdlow N.R. Human studies of prepulse inhibition of startle: normal subjects, patient groups, and pharmacological studies. Psychopharmacology 2001, 156:234-258.
15. Cadenhead K.S., Geyer M.A., Braff D.L. Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder. Am. J. Psychiatry 1993, 150:1862-1867.
16. Castellanos F.X., Fine E.J., Kaysen D., Marsh W.L., Rapoport J.L., Hallett M. Sensorimotor gating in boys with Tourette's syndrome and ADHD: preliminary results. Biol. Psychiatry 1996, 39:33-41.
17. Conti L.H., Berridge C.W., Tayler J.E. Both corticotropin-releasing factor and apomorphine reduce prepulse inhibition following repeated central infusion of corticotropin-releasing factor. Pharmacol. Biochem. Behav. 2006, 85:261-272. 2006.
18. Davis M., Aghajanian G.K. Effects of apomorphine and haloperidol on the acoustic startle response in rats. Psychopharmacology 1976, 47:217-223.
19. Davis M. Neurochemical modulation of sensory-motor reactivity: acoustic and tactile startle reflexes. Neurosci. Biobehav. Rev. 1980, 4:241-263.
20. Davis M., Mansbach R.S., Swerdlow N.R., Braff D.L., Geyer M.A. Apomorphine disrupts the inhibition of acoustic startle induced by weak prepulses in rats. Psychopharmacology 1990, 102:1-4.
21. Dazzi L., Serra M., Seu E., Cherchi G., Pisu M.G., Purdy R.H., Biggio G. Progesterone enhances ethanol-induced modulation of mesocortical dopamine neurons: antagonism by finasteride. J. Neurochem. 2002, 83:1103-1109.
22. Devoto P., Flore G. On the origin of cortical dopamine: is it a co-transmitter in noradrenergic neurons?. Curr. Neuropharmacol. 2006, 4:115-125.
23. Devoto P., Flore G., Saba P., Castelli M.P., Piras A.P., Luesu W., Viaggi M.C., Ennas M.G., Gessa G.L. 6-Hydroxydopamine lesion in the ventral tegmental area fails to reduce extracellular dopamine in the cerebral cortex. J. Neurosci. Res. 2008, 86:1647-1658.
24. Dluzen D.E., Green M.A., Ramirez V.D. The effect of hormonal condition on dose-dependent amphetamine-stimulated behaviors in the male rat. Horm. Behav. 1986, 20:1-6.
25. Dong E., Matsumoto K., Uzunov V., Sugaya I., Takahata H., Nomura H. Brain 5alpha-dihydroprogesterone and allopregnanolone synthesis in a mouse model of protracted social isolation. Proc. Natl. Acad. Sci. U.S.A. 2001, 98:2849-2854.
26. Elias A., Kumar A. Testosterone for schizophrenia. Cochrane Database Syst. Rev. 2007, 3:CD006197.
27. Engel J., Ahlenius S., Almgren O., Carlsson A., Larsson K., Södersten P. Effects of gonadectomy and hormone replacement on brain monoamine synthesis in male rats. Pharmacol. Biochem. Behav. 1979, 10:149-154.
28. Engin E., Treit D. The anxiolytic-like effects of allopregnanolone vary as a function of intracerebral microinfusion site: the amygdala, medial prefrontal cortex, or hippocampus. Behav. Pharmacol. 2007, 18:461-470.
29. Fabre-Nys C. Steroid control of monoamines in relation to sexual behaviour. Rev. Reprod. 1998, 3:31-41.
30. Frye C.A., Rhodes M.E., Rosellini R., Svare B. The nucleus accumbens as a site of action for rewarding properties of testosterone and its 5alpha-reduced metabolites. Pharmacol. Biochem. Behav. 2002, 74:119-127.
31. Geyer M.A., Krebs-Thomson K., Braff D.L., Swerdlow N.R. Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review. Psychopharmacology 2001, 156:117-154.
32. Gizerian S.S., Morrow A.L., Lieberman J.A., Grobin A.C. Neonatal neurosteroid administration alters parvalbumin expression and neuron number in medial dorsal thalamus of adult rats. Brain Res. 2004, 25:66-74.
33. Gogos A., van den Buuse M. Castration reduces the effect of serotonin-1A receptor stimulation on prepulse inhibition in rats. Behav. Neurosci. 2003, 117:1407-1415.
34. Goldstein J.M., Seidman L.J., O'Brien L.M., Horton N.J., Kennedy D.N., Makris N., Caviness V.S., Faraone V., Tsuang M.T. Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging. Arch. Gen. Psychiatry 2002, 59:154-164.
35. Goyal R.O., Sagar R., Ammini A.C., Khurana M.L., Alias A.G. Negative correlation between negative symptoms of schizophrenia and testosterone levels. Ann. N.Y. Acad. Sci. 2004, 1032:291-294.
36. Gras F., Brunmair B., Quarré L., Szöcs Z., Waldhäusl W., Fürnsinn C. Progesterone impairs cell respiration and suppresses a compensatory increase in glucose transport in isolated rat skeletal muscle: a non-genomic mechanism contributing to metabolic adaptation to late pregnancy?. Diabetologia 2007, 50:2544-2552.
37. Grobin A.C., Gizerian S., Lieberman J.A., Morrow A.L. Perinatal allopregnanolone influences prefrontal cortex structure, connectivity and behavior in adult rats. Neuroscience 2006, 138:809-819.
38. Gur R.E., Turetsky B.I., Cowell P.E., Finkelman C., Maany V., Grossman R.I., Arnold S.E., Bilker W.B., Gur R.C. Temporolimbic volume reductions in schizophrenia. Arch. Gen. Psychiatry 2000, 57:769-775.
39. Häfner H. Gender differences in schizophrenia. Psychoneuroendocrinology 2003, 28:17-54.
40. Halari R., Kumari V., Mehrotra R., Wheeler M., Hines M., Sharma T. The relationship of sex hormones and cortisol with cognitive functioning in schizophrenia. J. Psychopharmacol. 2004, 18:366-374.
41. Hart S., Zreik M., Carper R., Swerdlow N.R. Localizing haloperidol effects on sensorimotor gating in a predictive model of antipsychotic potency. Pharmacol. Biochem. Behav. 1998, 61:113-119.
42. Hernandez L., Gonzalez L., Murzi E., Paez X., Gottberg E., Baptista T. Testosterone modulates mesolimbic dopaminergic activity in male rats. Neurosci. Lett. 1994, 71:172-174.
43. Huber T.J., Tettenborn C., Leifke E., Emrich H.M. Sex hormones in psychotic men. Psychoneuroendocrinology 2005, 30:111-114.
44. Johansson C., Jackson D.M., Zhang J., Svensson L. Prepulse inhibition of acoustic startle, a measure of sensorimotor gating: effects of antipsychotics and other agents in rats. Pharmacol. Biochem. Behav. 1995, 52:649-654.
45. Kehne J.H., Sorenson C.A. The effects of pimozide and phenoxybenzamine pretreatments on amphetamine and apomorphine potentiation of the acoustic startle response in rats. Psychopharmacology 1978, 58:137-144.
46. Kinney G.G., Wilkinson L.O., Saywell K.L., Tricklebank M.D. Rat strain differences in the ability to disrupt sensorimotor gating are limited to the dopaminergic system, specific to prepulse inhibition, and unrelated to changes in startle amplitude or nucleus accumbens dopamine receptor sensitivity. J. Neurosci. 1999, 19:5644-5653.
47. Koethe D., Bortolato M., Piomelli D., Leweke F.M. Improvement of general symptoms in a chronic psychotic patient treated with finasteride: case report. Pharmacopsychiatry 2008, 41:115-116.
48. Kretschmer B.D., Koch M. The ventral pallidum mediates disruption of prepulse inhibition of the acoustic startle response induced by dopamine agonists, but not by NMDA antagonists. Brain Res. 1998, 798:204-210.
49. Kumari V., Antonova E., Geyer M.A., Ffytche D., Williams S.C., Sharma T. A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics. Int. J. Neuropsychopharmacol. 2007, 10:463-477.
50. Leumann L., Feldon J., Vollenweider F.X., Ludewig K. Effects of typical and atypical antipsychotics on prepulse inhibition and latent inhibition in chronic schizophrenia. Biol. Psychiatry 2002, 52:729-739.
51. Mansbach R., Geyer M.A., Braff D.L. Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 1988, 94:507-514.
52. Martini L., Melcangi R.C., Maggi R. Androgen and progesterone metabolism in the central and peripheral nervous system. J. Steroid Biochem. Mol. Biol. 1993, 47:195-205.
53. Marx C.E., Stevens R.D., Shampine L.J., Uzunova V., Trost W.T., Butterfield M.I., Massing M.W., Hamer R.M., Morrow A.L., Lieberman J.A. Neuroactive steroids are altered in schizophrenia and bipolar disorder: relevance to pathophysiology and therapeutics. Neuropsychopharmacology 2006, 31:1249-1263.
54. Menniti F.S., Baum M.J. Differential effects of estrogen and androgen on locomotor activity induced in castrated male rats by amphetamine, a novel environment, or apomorphine. Brain Res. 1981, 216:89-107.
55. Meredith G.E., Agolia R., Arts M.P., Groenewegen H.J., Zahm D.S. Morphological differences between projection neurons of the core and shell in the nucleus accumbens of the rat. Neuroscience 1992, 50:149-162.
56. Molina-Hernández M., Tellez-Alcántara N.P., García J.P., Lopez J.I., Jaramillo M.T. Antidepressant-like actions of intra-accumbens infusions of allopregnanolone in ovariectomized Wistar rats. Pharmacol. Biochem. Behav. 2005, 80:401-409.
57. Motzo C., Porceddu M.L., Maira G., Flore G., Concas A., Dazzi L., Biggio G. Inhibition of basal and stress-induced dopamine release in the cerebral cortex and nucleus accumbens of freely moving rats by the neurosteroid allopregnanolone. J. Psychopharmacol. 1996, 10:266-272.
58. Muroni A., Paba S., Puligheddu M., Marrosu F., Bortolato M. A preliminary study of finasteride in Tourette syndrome. Mov. Disord. 2011, 26:2146-2147.
59. Oren I., Fleishman S.J., Kessel A., Ben-Tal N. Free diffusion of steroid hormones across biomembranes: a simplex search with implicit solvent model calculations. Biophys. J. 2004, 87:768-779.
60. Paba S., Frau R., Godar S.C., Devoto P., Marrosu F., Bortolato M. Steroid 5α-reductase as a novel therapeutic target for schizophrenia and other neuropsychiatric disorders. Curr. Pharm. Des. 2011, 17:151-167.
61. Paxinos G., Watson C. The Rat Brain in Stereotaxic Coordinates 1998, Academic Press, New York.
62. Perry W., Minassian A., Feifel D., Braff D.L. Sensorimotor gating deficits in bipolar disorder patients with acute psychotic mania. Biol. Psychiatry 2001, 50:418-424.
63. Petitclerc M., Bedard P.J., Di Paolo T. Progesterone releases dopamine in male and female rat striatum: a behavioral and microdialysis study. Prog. Neuropsychopharmacol. Biol. Psychiatry 1995, 19:491-497.
64. Purdy R.H., Morrow A.L., Moore P.H., Paul S.M. Stress-induced elevations of gamma-aminobutyric acid type A receptor-active steroids in the rat brain. Proc. Natl. Acad. Sci. U.S.A. 1991, 15:4553-4557.
65. Putnam S.K., Sato S., Hull E.M. Effects of testosterone metabolites on copulation and medial preoptic dopamine release in castrated male rats. Horm. Behav. 2003, 44:419-426.
66. Rhodes M.E., Frye C.A. Inhibiting progesterone metabolism in the hippocampus of rats in behavioral estrus decreases anxiolytic behaviors and enhances exploratory and antinociceptive behaviors. Cogn. Affect. Behav. Neurosci. 2001, 1:287-296.
67. Rougé-Pont F., Mayo W., Marinelli M., Gingras M., Le Moal M., Piazza P.V. The neurosteroid allopregnanolone increases dopamine release and dopaminergic response to morphine in the rat nucleus accumbens. Eur. J. Neurosci. 2002, 16:169-173.
68. Rupprecht R., Holsboer F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci. 1999, 22:410-416.
69. Rupprecht R., Koch M., Montkowski A., Lancel M., Faulhaber J., Harting J., Spanagel R. Assessment of neuroleptic-like properties of progesterone. Psychopharmacology 1999, 143:29-38.
70. Saalmann Y.B., Kirkcaldie M.T., Waldron S., Calford M.B. Cellular distribution of the GABA-A receptor-modulating 3alpha-hydroxy, 5alpha-reduced pregnane steroids in the adult rat brain. J. Neuroendocrinol. 2007, 19:272-284.
71. Santana N., Mengod G., Artigas F. Quantitative analysis of the expression of dopamine D1 and D2 receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb. Cortex 2009, 19:849-860.
72. Savageau M.M., Beatty W.W. Gonadectomy and sex differences in the behavioral responses to amphetamine and apomorphine of rats. Pharmacol. Biochem. Behav. 1981, 14:17-21.
73. Shilliam C.S., Heidbreder C.A. Gradient of dopamine responsiveness to dopamine receptor agonists in subregions of the rat nucleus accumbens Eur. J. Pharmacol. 2003, 477:113-122.
74. Seeman M.V. Gender differences in the prescribing of antipsychotic drugs. Am. J. Psychiatry 2004, 161:1324-1333.
75. Stojanov W., Karayanidis F., Johnston P., Bailey A., Carr V., Schall U. Disrupted sensory gating in pathological gambling. Biol. Psychiatry 2003, 54:474-484.
76. Swerdlow N.R., Braff D.L., Lehmann-Masten V., Geyer M.A. Schizophrenic-like sensorimotor gating abnormalities in rats following dopamine infusion into the nucleus accumbens. Psychopharmacology 1990, 101:414-420.
77. Swerdlow N.R., Caine S.B., Geyer M.A. Regionally selective effects of intracerebral dopamine infusion on sensorimotor gating of the startle reflex in rats. Psychopharmacology 1992, 108:189-195.
78. Swerdlow N.R., Geyer M.A. Clozapine and haloperidol in an animal model of sensorimotor gating deficits in schizophrenia. Pharmacol. Biochem. Behav. 1993, 44:741-744.
79. Swerdlow N.W., Lipska B.K., Jaskin G.E., Geyer M.A. Increased sensitivity to the sensorimotor gating-disruptive effects of apomorphine after lesions of medial prefrontal cortex or ventral hippocampus in adult rats. Psychopharmacology 1995, 122:27-34.
80. Swerdlow N.R., Martinez Z.A., Hanlon F.M., Platten A., Farid M., Auerbach P., Braff D.L., Geyer M.A. Toward understanding the biology of a complex phenotype: rat strain and substrain differences in the sensorimotor gating-disruptive effects of dopamine agonists. J. Neurosci. 2000, 20:4325-4336.
81. Swerdlow N.R., Taaid N., Halim N., Randolph E., Kim Y.K., Auerbach P. Hippocampal lesions enhance startle gating-disruptive effects of apomorphine in rats: a parametric assessment. Neuroscience 2000, 96:523-536.
82. Swerdlow N.R., Platten A., Kim Y.K., Gaudet I., Shoemaker J., Pitcher L., Auerbach P. Sensitivity to the dopaminergic regulation of prepulse inhibition in rats: evidence for genetic, but not environmental determinants. Pharmacol. Biochem. Behav. 2001, 70:219-226.
83. Swerdlow N.R., Geyer M.A., Braff D.L. Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges. Psychopharmacology 2001, 156:194-215.
84. Taherianfard M., Shariaty M. Evaluation of serum steroid hormones in schizophrenic patients. Indian J. Med. Sci. 2004, 58:3-9.
85. Tamminga C.A. Gender and schizophrenia. J. Clin. Psychiatry 1997, 58:33-37.
86. Tanner C.M., Goldman S.M. Epidemiology of Tourette syndrome. Neurol. Clin. 1997, 15:395-402.
87. Thigpen A.E., Russell D.W. Four-amino acid segment in steroid 5 alpha-reductase 1 confers sensitivity to finasteride, a competitive inhibitor. J. Biol. Chem. 1992, 267:8577-8583.
88. Thompson T.L., Moss R.L. Estrogen regulation of dopamine release in the nucleus accumbens: genomic- and nongenomic-mediated effects. J. Neurochem. 1994, 62:1750-1756.
89. Turvin J.C., Messer W.S., Kritzer M.F. On again, off again effects of gonadectomy on the acoustic startle reflex in adult male rats. Physiol. Behav. 2007, 90:473-482.
90. van Winkel R., Stefanis N.C., Myin-Germeys I. Psychosocial stress and psychosis. A review of the neurobiological mechanisms and the evidence for gene-stress interaction. Schizophr. Bull. 2008, 34:1095-1105.
91. Wan F.J., Geyer M.A., Swerdlow N.R. Accumbens D2 modulation of sensorimotor gating in rats: assessing anatomical localization. Pharmacol. Biochem. Behav. 1994, 49:155-163.
92. Wan F.J., Taaid N., Swerdlow N.R. Do D1/D2 interactions regulate prepulse inhibition in rats?. Neuropsychopharmacology 1996, 14:265-274.
93. Wong J., Shoemaker J.M., Platten A., Martinez Z.A., Pitcher L., Hakimzada F., Auerbach P., Swerdlow N.R. Atypical antipsychotic effects on startle gating in adult rats: lack of sex difference and impact of prepubertal castration. Abstr. Biol. Psychiatry 2002, 51:120S.
94. Young K.A., Randall P.K., Wilcox R.E. Dose and time response analysis of apomorphine's effect on prepulse inhibition of acoustic startle. Behav. Brain Res. 1991, 42:43-48.