Journal of Molecular Neuroscience

, Volume 18, Issue 1–2, pp 151–165

Evaluation of an anxiety-related phenotype in galanin overexpressing transgenic mice

  • Andrew Holmes
  • Rebecca J. Yang
  • Jacqueline N. Crawley
Protein Processing And Trafficking, Pain, Depression, And Anxiety


Understanding the role of neuropeptides in mediating emotional behaviors is an important avenue for discovering novel drug targets for anxiety disorders. A role for galanin in mediating anxiety-related behavior is suggested by the pattern of distribution in the CNS and the coexistence of galanin with norepinephrine in the locus coeruleus. Studies in rats have shown that central administration of galanin modulates anxiety-related behaviors, and galanin release blocks the proanxiety effects of noradrenergic activation in prestressed rats. To further investigate the role of galanin in anxiety behaviors, we conducted a comprehensive behavioral phenotyping of galanin overexpressing transgenic mice (GAL-tg). GAL-tg mice were normal on measures of general health, neurological reflexes, home cage social behaviors, sensory functions, motor coordination, and exploratory locomotor activity. In three separate tests for anxiety-related behaviors, the elevated plus-maze, light ↔ dark exploration, and open field center time, GAL-tg mice showed no anxiety-like phenotype. GAL-tg mice and wildtype littermate controls were equally responsive to the anxiolytic effects of chlordiazepoxide (10 mg/kg) in the light ↔ dark exploration test, indicating normal benzodiazepine receptor function in GAL-tg mice. Stimulation of noradrenergic cells via administration with an α2 adrenoreceptor antagonist, yohimbine (2.5 mg/kg), produced proanxiety effects in wild type mice in the light ↔ dark exploration test, but not in the GAL-tg mice. These data suggest that galanin contributes to the modulation of anxiety states induced by high levels of noradrenergic activation, but is silent under less challenging situations. A specific role for galanin in extreme anxiety states represents an attractive target for the development of novel anxiolytic treatments.

Index Entries

Galanin anxiety stress multitiered strategy transgenic mice norepinephrine yohimbine chlordiazepoxide elevated plus-maze light ↔ dark exploration test 


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  1. Aggleton J. P. (1993) The contribution of the amygdala to normal and abnormal emotional states. Trends Neurosci. 16, 328–333.PubMedCrossRefGoogle Scholar
  2. American Psyciatric Association (1994) DSM-IV, American Psychiatric Press, Washington DC.Google Scholar
  3. Austin M. C., Cottingham S. L., Paul S. M., and Crawley J. N. (1990) Tyrosine hydroxylase and galanin mRNA levels in locus coeruleus neurons are increased following reserpine administration. Synapse 6, 351–357.PubMedCrossRefGoogle Scholar
  4. Bale T. L., Contarino A., Smith G. W., et al. (2000) Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat. Genet. 24, 410–414.PubMedCrossRefGoogle Scholar
  5. Bale T. L., Picetti R., Contarino A., et al. (2001) Mice deficient for both corticotropin-releasing factor receptor 1 (CRFR1) and CRFR2 have an impaired stress response and display sexually dichotomous anxiety-like behavior. J. Neurosci. 22, 193–199.Google Scholar
  6. Bartfai T., Fisone G., and Langel Ü. (1992) Galanin and galanin antagonists: molecular and biochemical perspectives. Trends Pharmacol. Sci. 13, 312–317.PubMedCrossRefGoogle Scholar
  7. Beal M. F., Clevens R. A., Chattha G. K., MacGarvey U. M., Mazurek M. F., and Gabriel S. M. (1988) Galaninlike immunoreactivity is unchanged in Alzheimer’s disease and Parkinson’s disease dementia cerebral cortex. J. Neurochem. 51, 1935–1941.PubMedCrossRefGoogle Scholar
  8. Belzung C., Le Guisquet A. M., and Crestani F. (2000) Flumazenil induces benzodiazepine partial agonist-like effects in BALB/c but not C57BL/6 mice. Psychopharmacology 148, 24–32.PubMedCrossRefGoogle Scholar
  9. Benzing W. C., Kordower J. H., and Mufson E. J. (1993) Galanin immunoreactivity within the primate basal forebrain: evolutionary change between monkeys and apes. J. Comp. Neurol. 336, 31–39.PubMedCrossRefGoogle Scholar
  10. Bing O., Möller C., Engel J. A., Soderpal B., and Heilig M. (1993) Anxiolytic-like action of centrally administered galanin. Neurosci. Lett. 164, 17–20.PubMedCrossRefGoogle Scholar
  11. Blakeman K. H., Holmberg K., Hao J. X., et al. (2001) Mice over-expressing galanin have elevated heat nociceptive threshold. Neuroreport 12, 423–425.PubMedCrossRefGoogle Scholar
  12. Bloch G. J., Butler P. C., and Kohlert J. G. (1996) Galanin microinjected into the medial preoptic nucleus facilitates female- and male-typical sexual behaviors in the female rat. Physiol. Behav. 59, 1147–1154.PubMedCrossRefGoogle Scholar
  13. Bloch G. J., Butler P. C., Eckersell C. B., and Mills R. H. (1998) Gonadal steroid-dependent GAL-IR cells within the medial preoptic nucleus (MPN) and the stimulatory effects of GAL within the MPN on sexual behaviors. Ann. N. Y. Acad. Sci. 863, 188–205.PubMedCrossRefGoogle Scholar
  14. Bowser R., Kordower J. H., and Mufson E. J. (1997) A confocal microscopic analysis of galaninergic hyperinnervation of cholinergic basal forebrain neurons in Alzheimer’s disease. Brain Pathol. 7, 723–730.PubMedGoogle Scholar
  15. Branchek T. A., Smith K. E., Gerald I., and Walker M. W. (2000) Galanin receptor subtypes. Trends Pharmacol. Sci. 21, 109–117.PubMedCrossRefGoogle Scholar
  16. Branchek T., Smith K. E., and Walker M. W. (1998) Molecular biology and pharmacology of galanin receptors. Ann. N. Y. Acad. Sci. 863, 94–107.PubMedCrossRefGoogle Scholar
  17. Bremner J. D., Krystal J. H., Southwick S. M., and Charney D. S. (1996a) Noradrenergic mechanisms in stress and anxiety: I. Preclinical studies. Synapse 23, 28–38.PubMedCrossRefGoogle Scholar
  18. Bremner J. D., Krystal J. H., Southwick S. M., and Charney D. S. (1996b) Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 23, 39–51.PubMedCrossRefGoogle Scholar
  19. Ceresini G., Marchini L., Fabbo A., et al. (1997) Evaluation of circulating galanin levels after exercise-induced pituitary hormone secretion in man. Metabolism 46, 282–286.PubMedCrossRefGoogle Scholar
  20. Chan-Palay V. (1998) Galanin hyperinnervates surviving neurons of the human basal nucleus of Meynert in dementias of Alzheimer’s and Parkinson’s disease: a hypothesis for the role of galanin in accentuating cholinergic dysfunction in dementia. J. Comp. Neurol. 273, 543–557.CrossRefGoogle Scholar
  21. Chan-Palay V. (1991) Alterations in the locus coeruleus in dementias of Alzheimer’s and Parkinson’s disease. Prog. Brain. Res. 88, 625–630.PubMedCrossRefGoogle Scholar
  22. Cheung C. C., Hohmann J. G., Clifton D. K., and Steiner R. A. (2001) Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus. Neuroscience 103, 423–432.PubMedCrossRefGoogle Scholar
  23. Cole J. C., Burroughs G. J., Laverty C. R., Sheriff N. C., Sparham E. A., and Rodgers R. J. (1995) Anxiolytic-like effects of yohimbine in the murine plus-maze: strain independence and evidence against alpha 2-adrenoceptor mediation. Psychopharmacology 118, 425–436.PubMedCrossRefGoogle Scholar
  24. Consolo S., Baldi G., Russi G., Civenni G., Bartfai T., and Vezzani A. (1994) Impulse flow dependency of galanin release in vivo in the rat ventral hippocampus. Proc. Natl. Acad. Sci. USA 91, 8047–8051.PubMedCrossRefGoogle Scholar
  25. Contarino A., Heinrichs S. C., and Gold L. H. (1999) Understanding corticotropin releasing factor neurobiology: contributions from mutant mice. Neuropeptides 33, 1–12.PubMedCrossRefGoogle Scholar
  26. Cortes R., Ceccatelli S., Schalling M., and Hökfelt T. (1990) Differential effects of intracerebroventricular colchicine administration on the expression of mRNAs for neuropeptides and neurotransmitter enzymes, with special emphasis on galanin: an in situ hybridization study. Synapse 6, 369–391.PubMedCrossRefGoogle Scholar
  27. Corwin R. L., Robinson J. K., and Crawley J. N. (1993) Galanin antagonists block galanin-induced feeding in the hypothalamus and amygdala of the rat. Eur. J. Neurosci. 5, 1528–1533.PubMedCrossRefGoogle Scholar
  28. Crabbe J. C., Wahlsten D., and Dudek B. C. (1999) Genetics of mouse behavior: interactions with laboratory environment. Science 284, 670–672.CrossRefGoogle Scholar
  29. Crawley J. N. (1981) Neuropharmacologic specificity of a simple animal model for the behavioral actions of benzodiazepines. Pharmacol. Biochem. Behav. 15, 695–699.PubMedCrossRefGoogle Scholar
  30. Crawley J. N. (1999a) Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. Brain Res. 835, 18–26.PubMedCrossRefGoogle Scholar
  31. Crawley J. N. (1999b) The role of galanin in feeding behavior. Neuropeptides 33, 369–375.PubMedCrossRefGoogle Scholar
  32. Crawley J. N. (2000) What Wrong with My Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice, Wiley-Liss, New York.Google Scholar
  33. Crawley J. N., Austin M. C., Fiske S. M., et al. (1990) Activity of centrally administered galanin fragments on stimulation of feeding behavior and on galanin receptor binding in the rat hypothalamus. J. Neurosci. 10, 695–3700.Google Scholar
  34. Crawley J. N. and Goodwin F. K. (1980) Preliminary report of a simple animal behavior model for the anxiolytic effects of benzodiazepines. Pharmacol. Biochem. Behav. 13, 167–170.PubMedCrossRefGoogle Scholar
  35. Crawley J. N. and Paylor R. (1997) A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm. Behav. 31, 197–211.PubMedCrossRefGoogle Scholar
  36. Crawley J. N., Robinson J. K., Langel Ü., and Bartfai T. (1993) Galanin receptor antagonists M40 and C7 block galanin-induced feeding. Brain Res. 600, 268–272.PubMedCrossRefGoogle Scholar
  37. Davis M. (1997) Neurobiology of fear responses: the role of the amygdala. J. Neuropsychiatry Clin. Neurosci. 9, 382–402.PubMedGoogle Scholar
  38. Degli Uberti E. C., Ambrosio M. R., Bondanelli M., et al. (1995) Human galanin reduces plasma norepinephrine levels in man. J. Clin. Endocrinol. Metab. 80, 1894–1898.PubMedCrossRefGoogle Scholar
  39. Diaz-Cabiale Z., Narvaez J. A., Garcia-Coronel M., and Fuxe K. (2001) Galanin/alpha2-adrenoceptor interactions in telencephalic and diencephalic regions of the rat. Neuroreport 12, 151–155.PubMedCrossRefGoogle Scholar
  40. Diaz-Cabiale Z., Narvaez J. A., Marcos P., et al. (1998) Galanin and NH2-terminal galanin fragments in central cardiovascular regulation. Ann. N. Y. Acad. Sci. 863, 421–424.PubMedCrossRefGoogle Scholar
  41. Edwards A. V., Jarhult J., Anderson P.-O., and Bloom S. R. (1982) The importance of the pattern of stimulation in relation to the response of automatic effectors, in Systemic Role of Regulatory Peptides, Bloom, S. R. and Polak J. M. (eds.), Lindenlaub., Schattauer, Stuttgart, pp. 145–148.Google Scholar
  42. Fathi Z., Cunningham A. M., Iben L. G., et al. (1997) Cloning, pharmacological characterization and distribution of a novel galanin receptor. Brain Res. Mol. Brain Res. 51, 49–59.PubMedCrossRefGoogle Scholar
  43. Foster O. J., Chowdrey H. S., Larsen P. J., and Lightman S. L. (1992) Differential regulation of tyrosine hydroxylase, neuropeptide Y and galanin gene expression in the pons and medulla oblong at a following chronic oral administration of 2% saline: a combined in situ hybridisation and immunohistochemical study. Neuroendocrinology 55, 544–551.PubMedGoogle Scholar
  44. Gentleman S. M., Falkai P., Bogerts B., Herrero M. T., Polak J. M., and Roberts G. W. (1989) Distribution of galanin-like immunoreactivity in the human brain. Brain Res. 505, 311–315.PubMedCrossRefGoogle Scholar
  45. Gray T. S. and Magnuson D. J. (1987) Galanin-like immunoreactivity within amygdaloid and hypothalamic neurons that project to the midbrain central grey in rat. Neurosci. Lett. 83, 264–268.PubMedCrossRefGoogle Scholar
  46. Griebel G. (1999) Is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders? Pharmacol. Ther. 82, 1–61.PubMedCrossRefGoogle Scholar
  47. Gustafson E. L., Smith K. E., Durkin M. M., Gerald C., and Branchek T. A. (1996) Distribution of a rat galanin receptor mRNA in rat brain. Neuroreport 7, 953–957.PubMedCrossRefGoogle Scholar
  48. Hasenohrl R. U., Souza-Silva M. A., Nikolaus S., et al. (2000) Substance P and its role in neural mechanisms governing learning, anxiety and functional recovery. Neuropeptides 34(5), 272–280.PubMedCrossRefGoogle Scholar
  49. Hedlund P. B. and Fuxe K. (1996) Galanin and 5-HT1A receptor interactions as an integrative mechanism in 5-HT neurotransmission in the brain. Ann. N.Y. Acad. Sci. 780, 193–212.PubMedCrossRefGoogle Scholar
  50. Heilig M. and Widerlov E. (1995) Neurobiology and clinical aspects of neuropeptide Y. Crit. Rev. Neurobiol. 9, 115–136.PubMedGoogle Scholar
  51. Hogg S. A. (1996) Review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol. Biochem. Behav. 54, 21–30.PubMedCrossRefGoogle Scholar
  52. Hökfelt T., Millhorn D., Seroogy K., et al. (1987) Coexistence of peptides with classical transmitters. Experientia 43, 768–780.PubMedCrossRefGoogle Scholar
  53. Hökfelt T., Bartfai T., and Crawley J.N. (1998a) Galanin: Basic research discoveries and therapeutic implications. Ann. N. Y. Acad. Sci. 863, xiii-xiv.CrossRefGoogle Scholar
  54. Hökfelt T., Xu Z. Q., Shi T. J., Holmberg K., and Zhang X. (1998b) Galanin in ascending systems. Focus on coexistence with 5-hydroxytryptamine and noradrenaline. Ann. N. Y. Acad. Sci. 863, 252–263.PubMedCrossRefGoogle Scholar
  55. Holets V. R., Hökfelt T., Rokaeus A., Terenius L., and Goldstein, M. (1988) Locus coeruleus neurons in the rat containing neuropeptide Y, tyrosine hydroxylase or galanin and their efferent projections to the spinal cord, cerebral cortex and hypothalamus. Neuroscience 24, 893–906.PubMedCrossRefGoogle Scholar
  56. Holmes A. (2001) Targeted gene mutation approaches to the study of anxiety-like behavior in mice. Neurosci. Biobehav. Rev. 25, 261–273.PubMedCrossRefGoogle Scholar
  57. Holmes P. V., Blanchard D. C., Blanchard R. J., Brady L. S., and Crawley J. N. (1995) Chronic social stress increases levels of preprogalanin mRNA in the rat locus coeruleus. Pharmacol. Biochem. Behav. 50, 655–660.PubMedCrossRefGoogle Scholar
  58. Holmes P. V. and Crawley J. N. (1995) Coexisting neurotransmitters in central noradrenergic neurons, In Psychopharmacology: The Fourth Generation of Progress (Bloom F. E. and Kupfer D. J., eds., Raven Press, New York, pp. 347–353.Google Scholar
  59. Holmes A., Hollon T. R., Liu Z., Sibley D. R., J. Dreiling, Gleason T. C., and Crawley, J. N. (2001) Dopamine D5 receptor null mutant mice show attenuated behavioral responses to a dopamine agonist. Behavioral Neuroscience 115, 1129–1144.PubMedCrossRefGoogle Scholar
  60. Holmes A., Parmigiani S., Ferrari P. F., Palanza P., and Rodgers R. J. (2000) Behavioral profile of wild mice in the elevated plus-maze test for anxiety. Physiol. Behav. 71, 509–516.PubMedCrossRefGoogle Scholar
  61. Holmes A. and Rodgers R. J. (1998) Responses of Swiss-Webster mice to repeated plus-maze experience: further evidence for a qualitative shift in emotional state? Pharmacol. Biochem. Behav. 60, 473–488.PubMedCrossRefGoogle Scholar
  62. Holmes A. and Rodgers R. J. (1999) Influence of spatial and temporal manipulations on the anxiolytic efficacy of chlordiazepoxide in mice previously exposed to the elevated plus-maze. Neurosci. Biobehav. Rev. 23, 971–980.PubMedCrossRefGoogle Scholar
  63. Holmes A. and Rodgers R. J. (2001) Prior test experience abolishes the anxiolytic efficacy of chlordiazepoxide in the mouse light/dark exploration test. Behav. Brain Res. 122, 159–167.PubMedCrossRefGoogle Scholar
  64. Iismaa T. P. and Shine J. (1999) Galanin and galanin receptors. Results Probl. Cell Differ. 26, 257–291.PubMedGoogle Scholar
  65. Kerr B. J., Cafferty W. B., Gupta Y. K., et al. (2000) Galanin knockout mice reveal nociceptive deficits following peripheral nerve injury. Eur. J. Neurosci. 12, 793–802.PubMedCrossRefGoogle Scholar
  66. Khoshbouei H., Cecchi M., and Morilak D. A. (1999) Interactive effects of acute stress and yohimbine on anxiety as measured with the elevated plus-maze. Soc. Neurosci. Abs. 25, 2140.Google Scholar
  67. Kishimoto T., Radulovic J., Radulovic M., et al. (2000) Deletion of crhr2 reveals an anxiolytic role for corticotropin-releasing hormone receptor-2. Nat. Genet. 24, 415–419.PubMedCrossRefGoogle Scholar
  68. Kiss A. and Jezova D. (1998) Stress and colchicine do not induce the release of galanin from the external zone of the median eminence. Histochem. J. 30, 569–575.PubMedCrossRefGoogle Scholar
  69. Koegler F. H., York D. A., and Bray G. A. (1999) The effects on feeding of galanin and M40 when injected into the nucleus of the solitary tract, the lateral parabrachial nucleus, and the third ventricle. Physiol. Behav. 67, 259–267.PubMedCrossRefGoogle Scholar
  70. Koob G. F. (1999) Corticotropin-releasing factor, norepinephrine, and stress. Biol. Psychiatry 46, 1167–1180.PubMedCrossRefGoogle Scholar
  71. Kyrkouli S. E., Stanley B. G., and Leibowitz S. F. (1986) Galanin: stimulation of feeding induced by medial hypothalamic injection of this novel peptide. Eur. J. Pharmacol. 122, 159–160.PubMedCrossRefGoogle Scholar
  72. Kyrkouli S. E., Stanley B. G., and Leibowitz S. F. (1992) Differential effects of galanin and neuropeptide Y on extracellular norepinephrine levels in the paraventricular hypothalamic nucleus of the rat: a microdialysis study. Life Sci. 51, 203–210.PubMedCrossRefGoogle Scholar
  73. LeDoux J. (1998) Fear and the brain: where have we been, and where are we going? Biol. Psychiatry 44, 1229–1238.PubMedCrossRefGoogle Scholar
  74. Lundberg J. M., Hedlund B., Anggard A., et al. (1982) Co-storage of peptides and classical transmitters in neurons, in Systemic Role of regulatory Peptides (Bloom S. R. and Polak J. M., eds.), Lindenlaub., Schattauer, Stuttgart, pp. 93–111.Google Scholar
  75. Makino S., Asaba K., Nishiyama M., and Hashimoto K. (1999) Decreased type 2 corticotropin-releasing hormone receptor mRNA expression in the ventromedial hypothalamus during repeated immobilization stress. Neuroendocrinology 70, 160–167.PubMedCrossRefGoogle Scholar
  76. Mathis C., Paul S. M., and Crawley J. N. (1995) Characterization of benzodiazepine-sensitive behaviors in the A/J and C57BL/6J inbred strains of mice. Behav. Genet. 24, 171–180.CrossRefGoogle Scholar
  77. Mazarati A. M., Halaszi E., and Telegdy G. (1992) Anticonvulsive effects of galanin administered into the central nervous system upon the picrotoxin-kindled seizure syndrome in rats. Brain Res. 589, 164–166.PubMedCrossRefGoogle Scholar
  78. Mazarati A. M., Liu H., Soomets U., et al. (1998) Galanin modulation of seizures and seizure modulation of hippocampal galanin in animal models of status epilepticus. J. Neurosci. 18, 10,070–10,077.Google Scholar
  79. Mazarati A. M., Hohmann J. G., Bacon A., et al. (2000) Modulation of hippocampal excitability and seizures by galanin. J. Neurosci. 20, 6276–6281.PubMedGoogle Scholar
  80. McDonald M. P., Gleason T. C., Robinson J. K., and Crawley J. N. (1998) Galanin inhibits performance on rodent memory tasks. Ann. N. Y. Acad. Sci. 863, 305–322.PubMedCrossRefGoogle Scholar
  81. Melander T., Hökfelt T., and Rökaeus Å. (1986) Distribution of galanin-like immunoreactivity in the rat central nervous system. J. Comp. Neurol. 248, 475–517.PubMedCrossRefGoogle Scholar
  82. Melander T., Köhler C., Nilsson S., et al. (1988) Autoradiographic quantitation and anatomical mapping of 125I-galanin binding sites in the rat central nervous system. J. Comp. Neurol. 1, 213–233.Google Scholar
  83. Miller M. A., Kolb P. E., and Raskind M. A. (1997) GALR1 galanin receptor mRNA is co-expressed by galanin neurons but not cholinergic neurons in the rat basal forebrain. Brain Res. Mol. Brain Res. 52, 121–129.PubMedCrossRefGoogle Scholar
  84. Möller C., Sommer W., Thorsell A., and Heilig M. (1999) Anxiogenic-like action of galanin after intra-amygdala administration in the rat. Neuropsychopharmacology 21, 507–512.PubMedCrossRefGoogle Scholar
  85. Mufson E. J., Kahl U., Bowser R., Mash D. C., Kordower J. H., and Deecher D. C. (1998) Galanin expression within the basal forebrain in Alzheimer’s disease. Comments on therapeutic potential. Ann. N.Y. Acad. Sci. 863, 291–304.PubMedCrossRefGoogle Scholar
  86. Narvaez J. A., Diaz-Cabiale Z., Hedlund P.B., et al. (2000) The galanin receptor antagonist M40 blocks the central cardiovascular actions of the galanin N-terminal fragment (1–15). Eur. J. Pharmacol. 399, 197–203.PubMedCrossRefGoogle Scholar
  87. Nishibori M., Oishi R., Itoh Y., and Saeki K. (188) Galanin inhibits noradrenaline-induced accumulation of cyclic AMP in the rat cerebral cortex. J. Neurochem. 51, 1953–1955.Google Scholar
  88. O’Neal H. A., Van Hoomissen J. D., Holmes P. V., and Dishman R. K. (2001) Prepro-galanin messenger RNA levels are increased in rat locus coeruleus after treadmill exercise training. Neurosci. Lett. 299, 69–72.PubMedCrossRefGoogle Scholar
  89. Perez S. E., Wynick D., Steiner R. A., and Mufson E. J. (2001) Distribution of galaninergic immunoreactivity in the brain of the mouse. J. Comp. Neurol. 434, 158–185.PubMedCrossRefGoogle Scholar
  90. Pieribone V. A., Xu Z. Q., Zhang X., Grillner S., Bartfai T., and Hökfelt T. (1995) Galanin induces a hyperpolarization of norepinephrine-containing locus coeruleus neurons in the brainstem slice. Neuroscience 64, 861–874.PubMedCrossRefGoogle Scholar
  91. Potter E. (1998) Cardiovascular actions of galanin. Ann. N. Y. Acad. Sci. 863, 170–174.PubMedCrossRefGoogle Scholar
  92. Rökaeus Å., Melander T., Hökfelt T., et al. (1984) A galanin-like peptide in the central nervous system and intestine of the rat. Neurosci. Lett. 47, 161–166.PubMedCrossRefGoogle Scholar
  93. Seutin V., Verbanck P., Massotte L., and Dresse A. (1989) Galanin decreases the activity of locus coeruleus neurons in vitro. Eur. J. Pharmacol. 164, 373–376.PubMedCrossRefGoogle Scholar
  94. Sevcik J., Finta E. P., and Illes P. (1993) Galanin receptors inhibit the spontaneous firing of locus coeruleus neurones and interact with mu-opioid receptors. Eur. J. Pharmacol. 230, 223–230.PubMedCrossRefGoogle Scholar
  95. Shih C. D., Chan S. H., and Chan J. Y. (1996) Participation of endogenous galanin in the suppression of baroreceptor reflex response by locus coeruleus in the rat. Brain Res. 20, 76–82.CrossRefGoogle Scholar
  96. Shimada T., Matsumoto K., Osanai M., Matsuda H., Terasawa K., and Watanabe H. (1995) The modified light ↔ dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs. Gen. Pharmacol. 26, 205–210.PubMedGoogle Scholar
  97. Skofitsch G., Sills M. A., and Jacobowitz D. M. (1986) Autoradiographic distribution of 125I-galanin binding sites in the rat central nervous system. Peptides 7, 1029–1042.PubMedCrossRefGoogle Scholar
  98. Smith G. W., Aubry J. M., Dellu F., et al. (1998) Corticotropin releasing factor receptor 1-deficient mice display decreased anxiety, impaired stress response, and aberrant neuroendocrine development. Neuron 20, 1093–1102.PubMedCrossRefGoogle Scholar
  99. Soares J., Holmes P. V., Renner K. J., Edwards G. L., Bunnell B. N., and Dishman R. K. (1999) Brain noradrenergic responses to footshock after chronic activity-wheel running. Behav. Neurosci. 113, 558–566.PubMedCrossRefGoogle Scholar
  100. Steiner R. A., Hohmann J. G., Holmes A., et al. (2001) Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 98, 4184–4189.PubMedCrossRefGoogle Scholar
  101. Stenzel-Poore M. P., Heinrichs S. C., Rivest S., Koob G. F., and Vale W. W. (1994) Overproduction of corticotropin-releasing factor in transgenic mice: a genetic model of anxiogenic behavior. J. Neurosci. 14, 2579–2584.PubMedGoogle Scholar
  102. Sweerts B.W., Jarrott B., and Lawrence A. J. (1999) Expression of preprogalanin mRNA following acute and chronic restraint stress in brains of normotensive and hypertensive rats. Brain Res. Mol. Brain Res. 69, 113–123.PubMedCrossRefGoogle Scholar
  103. Timpl P., Spanagel R., Sillaber I., et al. (1998) Impaired stress response and reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor. Nat. Genet. 19, 162–166.PubMedCrossRefGoogle Scholar
  104. Tjurmina O. A., Goldstein D. S., Palkovits M., and Kopin I. J. Alpha2-adrenoceptor-mediated restraint of norepinephrine synthesis, release, and turnover during immobilization in rats. Brain Res. 826, 243–252.Google Scholar
  105. Tsuda K., Yokoo H., and Goldstein M. (1989) Neuropeptide Y and galanin in norepinephrine release in hypothalamic slices. Hypertension 14, 81–86.PubMedGoogle Scholar
  106. Tsuda K., Goldstein M., and Masuyama Y. (1990) Neuropeptide Y and galanin enhance the inhibitory effects of clonidine on norepinephrine release from medulla oblongata of rats. Am. J. Hypertens. 3, 800–802.PubMedGoogle Scholar
  107. Tsuda K., Tsuda S., Nishio I., Masuyama Y., and Goldstein M. (1992) Modulation of norepinephrine release by galanin in rat medulla oblongata. Hypertension 20, 361–366.PubMedGoogle Scholar
  108. van Megen H. J., Westenberg H. G., den Boer J. A., and Kahn R. S. (1995) Cholecystokinin in anxiety. Eur. Neuropsychopharmacol. 6, 263–280.Google Scholar
  109. Venault P., Jacquot F., Save E., Sara S., and Chapouthier G. (1993) Anxiogenic-like effects of yohimbine and idazoxan in two behavioral situations in mice. Life Sci. 52, 639–645.PubMedCrossRefGoogle Scholar
  110. Weiss J. M., Bonsall R. W., Demetrikopoulos M. K., Emery M. S., and West C. H. Galanin: a significant role in depression? Ann. N. Y. Acad. Sci. 863, 364–382.Google Scholar
  111. Wiesenfeld-Hallin Z., Villar M. J., and Hökfelt T. (1989) The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. Brain Res. 486, 205–213.PubMedCrossRefGoogle Scholar
  112. Wiesenfeld-Hallin Z., Xu X. J., Villar M. J., and Hökfelt T. (1990) Intrathecal galanin potentiates the spinal analgesic effect of morphine: electrophysiological and behavioural studies. Neurosci. Lett. 109, 217–221.PubMedCrossRefGoogle Scholar
  113. Wrenn C. C. and Crawley J. N. (2001) Pharmacological evidence supporting a role for galanin in cognition and affect. Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 283–299.PubMedCrossRefGoogle Scholar
  114. Xu X. J., Hökfelt T., Bartfai T., and Wiesenfeld-Hallin Z. (2000) Galanin and spinal nociceptive mechanisms: recent advances and therapeutic implications. Neuropeptides 34, 137–147.PubMedCrossRefGoogle Scholar
  115. Xu Z. Q., Shi T. J., and Hökfelt T. (1998a) Galanin/GMAP-and NPY-like immunoreactivities in locus coeruleus and noradrenergic nerve terminals in the hippocampal formation and cortex with notes on the galanin-R1 and -R2 receptors. J. Comp. Neurol. 392, 227–251.PubMedCrossRefGoogle Scholar
  116. Xu Z. Q., Zhang X., Pieribone V. A., Grillner S., and Hökfelt T. (1998b) Galanin-5-hydroxytryptamine interactions: electrophysiological, immunohistochemical and in situ hybridization studies on rat dorsal raphe neurons with a note on galanin R1 and R2 receptors. Neuroscience 87, 79–94.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • Andrew Holmes
    • 1
  • Rebecca J. Yang
    • 1
  • Jacqueline N. Crawley
    • 1
  1. 1.Section on Behavioral NeuropharmacologyNational Institute of Mental Health, NIHBethesdaUSA

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