Psychopharmacology

, Volume 178, Issue 2–3, pp 115–124 | Cite as

Neuropeptide expression in rats exposed to chronic mild stresses

  • Valeriy Sergeyev
  • Serguei Fetissov
  • Aleksander A. Mathé
  • Patricia A. Jimenez
  • Tamas Bartfai
  • Patrick Mortas
  • Laurent Gaudet
  • Jean-Luc Moreau
  • Tomas Hökfelt
Original Investigation

Abstract

To investigate a possible link between some neuropeptides and depression, we analyzed their mRNA levels in brains of rats exposed to chronic mild stresses (CMS; a stress-induced anhedonia model), a commonly used model of depression. Rats exposed for 3 weeks to repeated, unpredictable, mild stressors exhibited an increased self-stimulation threshold, reflecting the development of an anhedonic state, which is regarded as an animal model of major depression. In situ hybridization was employed to monitor mRNA levels of neuropeptide Y (NPY), substance P and galanin in several brain regions. In the CMS rats, NPY mRNA expression levels were significantly decreased in the hippocampal dentate gyrus but increased in the arcuate nucleus. The substance P mRNA levels were increased in the anterodorsal part of the medial amygdaloid nucleus, in the ventromedial and dorsomedial hypothalamic nuclei and the lateral hypothalamic area, whereas galanin mRNA levels were decreased in the latter two regions. These findings suggest a possible involvement of these three peptides in mechanisms underlying depressive disorders and show that similar peptide changes previously demonstrated in genetic rat models also occur in the present stress-induced anhedonia model.

Keywords

Depression Galanin Mood Neuropeptide Neuropeptide Y Substance P 

Abbreviations

CMS

Chronic mild stress

FRL

Flinders resistant line

FSL

Flinders sensitive line

NPY

Neuropeptide tyrosine (Y)

REM

Rapid eye movement

References

  1. Ayensu WK, Pucilowksi O, Mason GA, Overstreet DH, Rezyani AH, Janowsky DS (1995) Effects of chronic mild stress on serum complement activity, saccharin preference and corticosterone levels in Flinders lines of rats. Physiol Behav 57:165–169CrossRefPubMedGoogle Scholar
  2. Barden N, Daigle M, Picard V, Di Paolo T (1993) Perturbation of rat brain serotonergic systems results in an inverse relation between substance P and serotonin concentrations measured in discrete nuclei. J Neurochem 41:834–840Google Scholar
  3. Bellido I, Diaz-Cabiale Z, Jimenez-Vasquez PA, Andbjer B, Mathé AA, Fuxe K (2002) Increased density of galanin binding sites in the dorsal raphe in a genetic rat model of depression. Neurosci Lett 317:101–105CrossRefPubMedGoogle Scholar
  4. Bing O, Moller C, Engel JA, Söderpalm B, Heilig M (1993) Anxiolytic-like action of centrally administered galanin. Neurosci Lett 164:17–20CrossRefPubMedGoogle Scholar
  5. Brady LS, Smith MA, Gold PW, Herkenham M (1990) Altered expression of hypothalamic neuropeptide mRNAs in food-restricted and food-deprived rats. Neuroendocrinology 52:441–447PubMedGoogle Scholar
  6. Brodin E, Ögren S-O, Theodorsson-Norheim E (1987) Effects of subchronic treatment with imipramine, zimelidine and alaproclate on regional tissue levels of substance P-and neurokinin A/neurokinin B-like immunoreactivity in the brain and spinal cord of the rat. Neuropharmacology 26:581–590CrossRefPubMedGoogle Scholar
  7. Caberlotto L, Hurd YL (1999) Reduced neuropeptide Y mRNA expression in the prefrontal cortex of subjects with bipolar disorders. Neuroreport 10:1747–1750PubMedGoogle Scholar
  8. Caberlotto L, Fuxe K, Overstreet DH, Gerrard P, Hurd YL (1998) Alterations in neuropeptide Y and Y1 receptor mRNA expression in brains from an animal model of depression: region specific adaptation after fluoxetine treatment. Brain Res 59:58–65CrossRefGoogle Scholar
  9. Cheeta S, Ruigt G, van Proosdij J, Willner P (1997) Changes in sleep architecture following chronic mild stress. Biol Psychiatry 41:419–427CrossRefPubMedGoogle Scholar
  10. Conrad CD, McEwen BS (2000) Acute stress increases neuropeptide Y mRNA within the arcuate nucleus and hilus of the dentate gyrus. Mol Brain Res 79:102–109CrossRefPubMedGoogle Scholar
  11. Dagerlind Å, Friberg K, Bean A, Hökfelt T (1992) Sensitive mRNA detection using unfixed tissue: combined radioactive and non-radioactive in situ hybridization histochemistry. Histochemistry 98:39–49PubMedGoogle Scholar
  12. D’Aquila P, Brain PF, Willner P (1994) Effects of chronic mild stress in behavioral tests relevant to anxiety and depression. Physiol Behav 56:861–867CrossRefPubMedGoogle Scholar
  13. Davis M, Rainnie D, Cassell M (1994) Neurotransmission in the rat amygdala related to fear and anxiety. Trends Neurosci 17:208–214CrossRefPubMedGoogle Scholar
  14. Dubinsky B, Goldberg ME (1971) The effect of imipramine and selected drugs on attack elicited by hypothalamic stimulation in the cat. Neuropharmacology 10:537–545CrossRefPubMedGoogle Scholar
  15. Duncan GE, Breese GR, Criswell H, Stumpf WE, Mueller RA, Covey JB (1986) Effects of antidepressant drugs injected into the amygdala on behavioral responses of rats in the forced swim test. J Pharmacol Exp Ther 238:758–762PubMedGoogle Scholar
  16. Flood JF, Hernandez EN, Morley JE (1987) Modulation of memory processing by neuropeptide Y. Brain Res 421:280–290CrossRefPubMedGoogle Scholar
  17. Fuxe K, Jansson A, Diaz-Cabiale Z, Andersson A, Tinner B, Finnman U-B, Misane I, Razani H, Wang F-H, Agnati L, Ögren SO (1998) Galanin modulates 5-hydroxytryptamine functions. Focus on galanin fragments/5-hydroxytryptamine 1A receptor interactions in the brain. Ann NY Acad Sci 863:274–290PubMedGoogle Scholar
  18. Gehlert DR, Chronwall BM, Schafer MP, O’Donohue TL (1987) Localization of neuropeptide Y messenger ribonucleic acid in rat and mouse brain by in situ hybridization. Synapse 1:25–31PubMedGoogle Scholar
  19. Gorka Z, Moryl E, Papp M (1996) The effect of chronic mild stress on circadian rhythms in the locomotor activity of rats. Pharmacol Biochem Behav 54:229–234CrossRefPubMedGoogle Scholar
  20. Gruber SHM, Efendic S, Mathé AA (2004) Neuropeptide Y has antidepressant properties in a rat model of depression. Nord J Psychiatry 58:97Google Scholar
  21. Harlan RE, Garcia MM, Krause JE (1989) Cellular localization of substance P- and neurokinin A-encoding preprotachykinin mRNA in the female rat. J Comp Neurol 287:179–212PubMedGoogle Scholar
  22. Hashimoto H, Onishi H, Koide S, Kai T, Yamagami S (1996) Plasma neuropeptide Y in patients with major depressive disorder. Neurosci Lett 216:57–60CrossRefPubMedGoogle Scholar
  23. Heilig M, Widerlöv E (1995) Neurobiology and clinical aspects of neuropeptide Y. Crit Rev Neurobiol 9:115–136PubMedGoogle Scholar
  24. Heilig M, McLeod S, Brot M, Heinrich SC, Menzaghi F, Koob GF, Britton KT (1993) Anxiolytic-like action of neuropeptide Y: mediation by Y1 receptors in amygdala and dissociation from food intake effects. Neuropsychopharmacology 8:357–363PubMedGoogle Scholar
  25. Hökfelt T, Xu Z-Q D, Shi T-J, Holmberg K, Zhang X (1998) Galanin in ascending systems. Focus on 5-hydroxytryptamine and noradrenaline. Ann NY Acad Sci 863:252–263PubMedGoogle Scholar
  26. Holmes PV, Blanchard DC, Blanchard RJ, Brady LS, Crawley JN (1995) Chronic social stress increases levels of preprogalanin mRNA in the rat locus coeruleus. Pharmacol Biochem Behav 50:655–660CrossRefPubMedGoogle Scholar
  27. Horovitz ZP, Pialo JJ, High JP, Burke JC, Leaf RC (1966) Effects of drugs on the mouse-killing (muricide) test and its relationship to amygdaloid function. Int J Neuropharmacol 5:405–411CrossRefPubMedGoogle Scholar
  28. Husum H, Mathé AA (2002) Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes. Neuropsychopharmacology 27:756–764CrossRefPubMedGoogle Scholar
  29. Husum H, Mikkelsen JD, Hogg S, Mathé AA, Mörk A (2000) Involvement of hippocampal neuropeptide Y in mediating the chronic actions of lithium, electroconvulsive stimulation and citalopram. Neuropharmacology 39:1463–1473CrossRefPubMedGoogle Scholar
  30. Husum H, Jiménez-Vasquez PA, Mathé AA (2001) Changed concentrations of tachykinins and neuropeptide Y in brain of the rat model of depression: Lithium treatment normalizes tachykinins. Neuropsychopharmacology 24:183–191CrossRefPubMedGoogle Scholar
  31. Hökfelt T, Broberger C, Xu Z-Q, Sergeyev V, Ubink R, Diez M (2000) Neuropeptides—an overview. Neuropharmacology 39:1337–1356CrossRefPubMedGoogle Scholar
  32. Jacobowitz DM, Skofitsch G (1991) Localization of galanin cell bodies in the brain by immunocytochemistry and in situ hybridization histochemistry. In: Hökfelt T, Bartfai T, Jacobowitz D, Ottoson D (eds) Galanin. A new multifunctional peptide in the neuro-endocrine system. Wenner-Gren Center Int. Symp. Ser., vol 58. MacMillan, New York, pp 69–92Google Scholar
  33. Janowsky DS, Overstreet DH, Nurberger JI (1994) Is cholinergic sensitivity a genetic marker for the affective disorders? Am J Med Genet 54:335–344PubMedGoogle Scholar
  34. Jiménez Vasquez PA, Overstreet DH, Mathé AA (2000a) Neuropeptide Y in male and female brains of Flinders Sensitive Line, a rat model of depression. Effects of electroconvulsive stimuli. J Psychiatr Res 34:405–412CrossRefPubMedGoogle Scholar
  35. Jiménez Vasquez PA, Salmi P, Ahlenius S, Mathé AA (2000b) Neuropeptide Y in brains of the Flinders Sensitive Line rat, a model of depression. Effects of electroconvulsive stimuli and d-amphetamine on peptide concentrations and locomotion. Behav Brain Res 111:115–123CrossRefPubMedGoogle Scholar
  36. Kalin NH, Carnes M (1984) Biological correlates of attachment bond disruption in humans and nonhuman primates. Prog Neuropsychopharmacol Biol Psychiatry 8:459–469CrossRefPubMedGoogle Scholar
  37. Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J, Sramek JJ, Reines SA, Liu G, Snavely D, Wyatt-Knowles E, Hyde JJ, Mills SG, MacCoss M, Swain CJ, Harrison T, Hill RG, Hefti F, Scolnick EM, Cascieri MA, Chicchi GG, Sadowski S, Williams AR, Hewson L, Smith D, Carlson EJ, Hargreaves RJ, Rupniak NM (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281:1640–1645CrossRefPubMedGoogle Scholar
  38. Krause JE, Chirgwin JM, Carter MS, Xu ZS, Hershey AD (1987) Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc Natl Acad Sci U S A 84:881–885PubMedGoogle Scholar
  39. Ladd CO, Owens MJ, Nemeroff CB (1996) Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology 137:1212–1218CrossRefPubMedGoogle Scholar
  40. Larhammar D, Ericsson A, Persson H (1987) Structure and expression of the rat neuropeptide Y gene. Proc Natl Acad Sci U S A 84:2068–2072PubMedGoogle Scholar
  41. Makino S, Baker RA, Smith MA, Gold PW (2000) Differential regulation of neuropeptide Y mRNA expression in the arcuate nucleus and locus coeruleus by stress and antidepressants. J Neuroendocrinol 12:387–395CrossRefPubMedGoogle Scholar
  42. Mathé AA (1999) Neuropeptides and electroconvulsive treatment. J ECT 15:60–75PubMedGoogle Scholar
  43. Mathé AA, Jousisto-Hanson J, Stenfors C, Theodorsson E (1990) Effect of lithium on tachykinins, calcitonin gene-related peptide, and neuropeptide Y in rat brain. J Neurosci Res 26:233–237PubMedGoogle Scholar
  44. Mathé AA, Gruber S, Jimenez PA, Theodorsson E, Stenfors C (1997) Effect of electroconvulsive stimuli and MK-801 on neuropepride Y, neurokinin A, and calcitonin gene-related peptide in rat brain. Neurochem Res 22:629–636CrossRefPubMedGoogle Scholar
  45. Mathé AA, Jimenez PA, Theodorsson E, Stenfors C (1998) Neuropeptide Y, neurokinin A and neurotensin in brain regions of fawn hooded “depressed,” Wistar, and Sprague Dawley rats. Effects of electroconvulsive stimuli. Prog NeuroPsychopharmacol. Biol Psychiatry 22:529–546CrossRefPubMedGoogle Scholar
  46. McKibbin PE, McCarthy HD, Shaw P, Williams G (1992) Insulin deficiency is a specific stimulus to hypothalamic neuropeptide Y: a comparison of the effects of insulin replacement and food restriction in streptozocin-diabetic rats. Peptides 13:721–727CrossRefPubMedGoogle Scholar
  47. Melander T, Hökfelt T, Rökaeus Å, Cuello AC, Oertel WH, Verhofstad A, Goldstein M (1986) Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS. J Neurosci 6:3640–3654PubMedGoogle Scholar
  48. Mikkelsen JD, Woldbye D, Kragh J, Larsen P, Bowlig TG (1994) Electroconvulsive shocks increase the expression of neuropeptide Y (NPY) mRNA in the piriform cortex and the dentate gyrus. Mol Brain Res 23:317–322CrossRefPubMedGoogle Scholar
  49. Moller C, Sommer W, Thorsell A, Heilig M (1999) Anxiogenic-like action of galanin after intra-amygdala administration in the rat. Neuropsychopharmacology 21:507–512CrossRefPubMedGoogle Scholar
  50. Moreau JL, Jenck F, Martin JR, Mortas P, Haefely WE (1992) Antidepressant prevents chronic unpredictable mild stress-induced anhedonia as assessed by ventral tegmentum self-stimulation behavior in rats. Neuropsychopharmacology 2:43–49CrossRefGoogle Scholar
  51. Moreau JL, Jenck F, Martin JR, Mortas P (1994) Curative effects of the atypical antidepressant mianserin in the chronic mild stress-induced anhedonia model of depression. J Psychiatry Neurosci 19:51–56PubMedGoogle Scholar
  52. Moreau JL, Scherschlict R, Jenck F, Martin JR (1995) Chronic mild stress-induced anhedonia model of depression: sleep abnormalities and curative effects of electroshock treatment. Behav Pharmacol 6:682–687PubMedGoogle Scholar
  53. Moreau JL, Jenck F, Martin JR (1998) Simulation of a core symptom of human depression in rats. Curr Top Pharmacol 4:37–50Google Scholar
  54. Morley JE (1987) Neuropeptide regulation of appetite and weight. Endocr Rev 8:265–287Google Scholar
  55. Morley JE, Flood JF (1990) Neuropeptide Y and memory processing. Ann NY Acad Sci 611:226–231PubMedGoogle Scholar
  56. Morris JL, Gibbins IL (1989) Co-localization and plasticity of transmitters in peripheral autonomic and sensory neurons. Int J Dev Neurosci 7:521–531CrossRefPubMedGoogle Scholar
  57. Morris JS, Friston KJ, Buchel C, Frith CD, Young AW, Calder AJ, Dolan RJ (1998) A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain 121:47–57CrossRefPubMedGoogle Scholar
  58. Muscat R, Willner P (1992) Suppression of sucrose drinking by chronic mild unpredictable stress: a methodological analysis. Neurosci Biobehav Rev 16:507–517PubMedGoogle Scholar
  59. Nilsson C, Karlsson G, Blennow K, Heilig M, Ekman R (1996) Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients. Peptides 17:359–362CrossRefPubMedGoogle Scholar
  60. Overstreet DH (1993) The Flinders sensitive line rats: a genetic animal model of depression. Neurosci Behav Rev 17:51–68Google Scholar
  61. Palkovits M (2000) Stress-induced expression of co-localized neuropeptides in hypothalamic and amygdaloid neurons. Eur J Pharmacol 405:161–166CrossRefPubMedGoogle Scholar
  62. Pieribone V, Xu Z-Q, Zhang X, Grillner S, Bartfai T, Hökfelt T (1995) Galanin induces a hyperpolarization of norepinephrine-containing locus coeruleus neurons in the brainstem slice. Neuroscience 64:861–874CrossRefPubMedGoogle Scholar
  63. Plotsky PM, Meaney MJ (1993) Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats. Mol Brain Res 18:195–200CrossRefPubMedGoogle Scholar
  64. Redrobe JP, Dumont Y, Fournier A, Quirion R (2002) The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neuropsychopharmacology 26:615–624CrossRefPubMedGoogle Scholar
  65. Riley LA, Walker PD, Hart RP, Jonakait GM (1991) Alterations of preprotachykinin (PPT) mRNA in medullary raphe occur following manipulation of serotonin. Ann NY Acad Sci 632:455–456PubMedGoogle Scholar
  66. Rogan MT, LeDoux JE (1996) Emotion: systems, cells, synaptic plasticity. Cell 85:469–475CrossRefPubMedGoogle Scholar
  67. Seutin V, Verbanck P, Massotte L, Dresse A (1989) Galanin decreases the activity of locus coeruleus neurons in vitro. Eur J Pharmacol 164:373CrossRefPubMedGoogle Scholar
  68. Sevcik J, Finta EP, Illes P (1993) Galanin receptors inhibit the spontaneous firing of locus coeruleus neurones and interact with μ-opioid receptors. Eur J Pharmacol 230:223–230CrossRefPubMedGoogle Scholar
  69. Shaikh MB, Steinberg A, Siegel A (1993) Evidence that substance P is utilized in medial amygdaloid facilitation of defensive rage behavior in the cat. Brain Res 625:283–294CrossRefPubMedGoogle Scholar
  70. Shirayama Y, Mitsushio H, Takashima M, Ichikawa H, Takahashi K (1996) Reduction of substance P after chronic antidepressants treatment in the striatum, substantia nigra and amygdala of the rat. Brain Res 739:70–78CrossRefPubMedGoogle Scholar
  71. Smith OA, Astley CA, DeVito JL, Stein JM, Walsh KE (1980) Functional analysis of hypothalamic control of the cardiovascular responses accompanying emotional behavior. Fed Proc 39:2487–2494PubMedGoogle Scholar
  72. Smith OA, Astley CA, de Vito JL, Stein JM, Walsh KE (1990) Functional analysis of hypothalamic control of cardiovascular responses to emotion are located in lateral hypothalamus-perifornical region. Am J Physiol 259:R943–R954PubMedGoogle Scholar
  73. Stanley BG, Leibowitz SF (1985) Neuropeptide Y injected in the paraventricular hypothalamus: a power stimulant of feeding behavior. Proc Natl Acad Sci U S A 82:3940–3943PubMedGoogle Scholar
  74. Stanley BG, Kyrkouli S, Lampert S, Leibowitz SF (1986) Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides 7:1189–1192CrossRefPubMedGoogle Scholar
  75. Stenfors C, Theodorsson E, Mathé AA (1989) Effect of repeated electroconvulsive treatment on regional concentrations of tachykinins, neurotensin, vasoactive polypeptide, neuropeptide Y and galanin in rat brain. J Neurosci Res 24:445–450PubMedGoogle Scholar
  76. Swanson LW (1987) The hypothalamus. In: Swanson LW, Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy, vol 5. Elsevier, Amsterdam, pp 1–124Google Scholar
  77. Sweerts BW, Jarrott B, Lawrence AJ (1999) Expression of preprogalanin mRNA following acute and chronic restraint stress in brains of normotensive and hypertensive rats. Mol Brain Res 69:113–123CrossRefPubMedGoogle Scholar
  78. Tempel DL, Leibowitz SF (1994) Adrenal steroid receptors: interactions with brain neuropeptide systems in relation to nutrient intake and metabolism. Neuroendocrinology 6:479–501Google Scholar
  79. Vrontakis ME, Peden LM, Duckworth ML, Friesen HG (1987) Isolation and characterization of a complementary DNA (galanin) clone from estrogen-induced pituitary tumor messenger RNA. J Biol Chem 262:16755–16758PubMedGoogle Scholar
  80. Wahlestedt C, Blendy JA, Kellar KJ, Heilig M, Widerlöv E, Ekman R (1990) Electroconvulsive shocks increase the concentration of neocortical and hippocampal neuropeptide Y (NPY)-like immunoreactivity in the rat. Brain Res 507:65–68CrossRefPubMedGoogle Scholar
  81. Wahlestedt C, Pich EM, Koob GF, Yee F, Heilig M (1993) Modulation of anxiety and neuropeptide Y-Y1 receptors by antisense oligodeoxynucleotides. Science 259:528–531PubMedGoogle Scholar
  82. Wang J, Akabayashi A, Dourmashkin J, Yu H-J, Alexander T, Chae HJ, Leibowitz SF (1998) Neuropeptide Y in relation to carbohydrate intake, corticosterone and dietary obesity. Brain Res 802:75–88CrossRefPubMedGoogle Scholar
  83. Warden MK, Young III WS (1988) Distribution of cells containing mRNAs encoding substance P and neurokinin B in the rat central nervous system. J Comp Neurol 272:90–113PubMedGoogle Scholar
  84. Weiner ED, Mallat A, Papolos DF, Lachman HM (1992) Acute lithium treatment enhances neuropeptide Y gene expression in rat hippocampus. Mol Brain Res 12:209–214CrossRefPubMedGoogle Scholar
  85. Weiss JM, Bonsall RW, Demetrikopoulos MK, Emery MS, West CHK (1998) Galanin: a significant role in depression? Ann NY Acad Sci 863:364–382PubMedGoogle Scholar
  86. Whalen PJ, Rausch SL, Etcoff NL, McInerney SC, Lee MB, Jenike MA (1998) Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. J Neurosci 18:411–418PubMedGoogle Scholar
  87. Widerlöv E, Heilig M, Ekman R, Wahlestedt C. (1988) Possible relationship between neuropeptide Y (NPY) and major depression—evidence from human and animal studies. Nord Psykiatr Tidsskr 42:131–137Google Scholar
  88. Willner P, Owell A, Sampson D, Sophokleous S, Muscat R (1987) Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology 93:358–364CrossRefPubMedGoogle Scholar
  89. Xu Z-QD, Tong Y-G, Hökfelt T (2001) Galanin enhances noradrenaline-induced outward current on locus coeruleus noradrenergic neurons. NeuroReport 12(8):1779–1782CrossRefPubMedGoogle Scholar
  90. Zachrisson O, Mathé AA, Stenfors C, Lindefors N (1995a) Limbic effects of repeated electroconvulsive stimulation on neuropeptide Y and somatostatin mRNA expression in the rat brain. Mol Brain Res 31:71–85CrossRefPubMedGoogle Scholar
  91. Zachrisson O, Mathé AA, Stenfors C, Lindefors N (1995b) Region-specific effects of chronic lithium administration on neuropeptide Y and somatostatin mRNA expression in the rat brain. Neurosci Lett 194:89–92CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Valeriy Sergeyev
    • 1
  • Serguei Fetissov
    • 1
  • Aleksander A. Mathé
    • 2
  • Patricia A. Jimenez
    • 2
  • Tamas Bartfai
    • 3
    • 4
  • Patrick Mortas
    • 3
  • Laurent Gaudet
    • 3
  • Jean-Luc Moreau
    • 3
  • Tomas Hökfelt
    • 1
  1. 1.Department of NeuroscienceKarolinska InstitutetStockholmSweden
  2. 2.Department of Physiology and PharmacologyKarolinska InstitutetStockholmSweden
  3. 3.Pharmaceutical Division, Preclinical CNS ResearchF. Hoffmann-La Roche Ltd.BaselSwitzerland
  4. 4.The Harold Dorris Neurological InstituteThe Scripps InstituteLa JollaUSA

Personalised recommendations