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Urocortin 1 administered into the hypothalamic supraoptic nucleus affects open-field behaviour in rats

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Abstract

The presence of both Urocortin 1 (Ucn1) and corticotropin-releasing factor 2 receptors (CRF2R) in the hypothalamic supraoptic nucleus (SON) suggests that endogenous Ucn1 released within this brain area acts as a local signal that might be involved in the regulation of not only endocrine but also behavioural stress responses. To test this hypothesis, we monitored the effects induced by the administration of a range of doses of synthetic Ucn1 (0.001–1.0 μg) bilaterally into the SON of rats in the open field test (OFT). Ucn1 administration produced an inverted U-shaped dose–response curve on OFT behaviour, in particular the dose of 0.01 μg of Ucn1 significantly increased the number of rearing and grooming episodes without affecting locomotion. In addition, this dosage augmented also the latency to visit the centre of the open field. Pre-treatment with the CRF2R antagonist, astressin-2B (0.1 μg) normalized Ucn1 treatment-induced effects. These results suggest that Ucn1 released within the SON area interacts with CRF2R to control the state of arousal.

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References

  • Arima H, Aguilera G (2000) Vasopressin and oxytocin neurones of hypothalamic supraoptic and paraventricular nuclei co-express mRNA for type-1 and type-2 corticotropin-releasing hormone receptors. J Neuroendocrinol 12:833–842

    Article  CAS  PubMed  Google Scholar 

  • Arzt E, Holsboer F (2006) CRF signaling: molecular specificity for drug targeting in the CNS. Trends Pharmacol Sci 27:531–538

    Article  CAS  PubMed  Google Scholar 

  • Bakshi VP, Smith-Roe S, Newman SM, Grigoriadis DE, Kalin NH (2002) Reduction of stress-induced behavior by antagonism of corticotropin-releasing hormone 2 (CRH2) receptors in lateral septum or CRH1 receptors in amygdala. J Neurosci 22:2926–2935

    CAS  PubMed  Google Scholar 

  • Bale TL, Vale WW (2004) CRF and CRF receptors: role in stress responsivity and other behaviors. Annu Rev Pharmacol Toxicol 44:525–557

    Article  CAS  PubMed  Google Scholar 

  • Bale TL, Contarino A, Smith GW, Chan R, Gold LH, Sawchenko PE, Koob GF, Vale WW, Lee KF (2000) Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behaviour and are hypersensitive to stress. Nat Genet 24:410–414

    Article  CAS  PubMed  Google Scholar 

  • Bittencourt JC, Vaughan J, Arias C, Rissman RA, Vale WW, Sawchenko PE (1999) Urocortin expression in rat brain: evidence against a pervasive relationship of urocortin-containing projections with targets bearing type 2 CRF receptors. J Comp Neurol 415:285–312

    Article  CAS  PubMed  Google Scholar 

  • Bohus B, Urban I, van Wimersma Greidanus TB, de Wied D (1978) Opposite effects of oxytocin and vasopressin on avoidance behaviour and hippocampal theta rhythm in the rat. Neuropharmacology 17:239–247

    Article  CAS  PubMed  Google Scholar 

  • Engelmann M, Ludwig M, Landgraf R (1994) Simultaneous monitoring of intracerebral release and behavior: endogenous vasopressin improves social recognition. J Neuroendocrinol 6:391–395

    Article  CAS  PubMed  Google Scholar 

  • Engelmann M, Ludwig M, Singewald N, Ebner K, Sabatier N, Lubec G, Landgraf R, Wotjak CT (2001) Taurine selectively modulates the secretory activity of vasopressin neurons in conscious rats. Eur J Neurosci 14:1047–1055

    Article  CAS  PubMed  Google Scholar 

  • Engelmann M, Ebner K, Landgraf R, Wotjak CT (2006) Effects of Morris water maze testing on the neuroendocrine stress response and intrahypothalamic release of vasopressin and oxytocin in the rat. Horm Behav 50:496–501

    Article  CAS  PubMed  Google Scholar 

  • Fatima A, Wolf G, Engelmann M, Spina M (2006) Dose-dependent effects of urocortin administered into the hypothalamic supraoptic nucleus on feeding and motor behaviour in rats. In: FENS Vienna, Austria, 08 July–12 July

  • Greenberg N, Carr JA, Summers CH (2002) Causes and consequences of stress. Integr Comp Biol 42:508–516

    Article  Google Scholar 

  • Hall CS (1934) Emotional behavior in the rat I. Defecation and urination as measures of individual differences in emotionality. J Comp Psycolol 18:385–403

    Article  Google Scholar 

  • Hauger RL, Grigoriadis DE, Dallman MF, Plotsky PM, Vale WW, Dautzenberg FM (2003) International Union of Pharmacology. XXXVI. Current status of the nomenclature for receptors for corticotropin-releasing factor and their ligands. Pharmacol Rev 55:21–26

    Article  CAS  PubMed  Google Scholar 

  • Henry B, Vale W, Markou A (2006) The effect of lateral septum corticotropin-releasing factor receptor 2 activation on anxiety is modulated by stress. J Neurosci 26:9142–9152

    Article  CAS  PubMed  Google Scholar 

  • Jolles J, Rompa-Barenderg J, Gispen WH (1979) Novelty and grooming behavior in the rat. Behav Neural Biol 25:563–572

    Article  Google Scholar 

  • Kalueff AV, Tuohimaa P (2004) Grooming analysis algorithm for neurobehavioural stress research. Brain Res Brain Res Protoc 13:151–158

    Article  PubMed  Google Scholar 

  • Kalueff AV, Tuohimaa P (2005) The grooming analysis algorithm discriminates between different levels of anxiety in rats: potential utility for neurobehavioural stress research. J Neurosci Methods 143:169–177

    Article  PubMed  Google Scholar 

  • Keck ME (2006) Corticotropin-releasing factor, vasopressin and receptor systems in depression and anxiety. Amino Acids 31:241–250

    Article  CAS  PubMed  Google Scholar 

  • Kozicz T, Yanaihara H, Arimura A (1998) Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. J Comp Neurol 391:1–10

    Article  CAS  PubMed  Google Scholar 

  • Kulinskayaa E, Dollingerb MB (2007) Robust weighted one-way ANOVA: improved approximation and efficiency. J Stat Plan Inference 137:462–472

    Article  Google Scholar 

  • Lammers JH, Meelis W, Kruk MR, van der Poel AM (1987) Hypothalamic substrates for brain stimulation-induced grooming, digging and circling in the rat. Brain Res 418:1–19

    Article  CAS  PubMed  Google Scholar 

  • Landgraf R (2006) Neuropeptides in anxiety and depression. Amino Acids 31:211–213

    Article  CAS  PubMed  Google Scholar 

  • Landgraf R, Neumann ID (2004) Vasopressin and oxytocin release within the brain: a dynamic concept of multiple and variable modes of neuropeptide communication. Front Neuroendocrinol 25:150–176

    Article  CAS  PubMed  Google Scholar 

  • Ludwig M, Leng G (2006) Dendritic peptide release and peptide-dependent behaviours. Nat Rev Neurosci 7:126–136

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. Academic Press, San Diego

    Google Scholar 

  • Pernar L, Curtis AL, Vale WW, Rivier JE, Valentino RJ (2004) Selective activation of corticotropin-releasing factor-2 receptors on neurochemically identified neurons in the rat dorsal raphe nucleus reveals dual actions. J Neurosci 24:1305–1311

    Article  CAS  PubMed  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

    Article  CAS  PubMed  Google Scholar 

  • Reyes BA, Fox K, Valentino RJ, Van Bockstaele EJ (2006) Agonist-induced internalization of corticotropin-releasing factor receptors in noradrenergic neurons of the rat locus coeruleus. Eur J Neurosci 23:2991–2998

    Article  PubMed  Google Scholar 

  • Risbrough VB, Hauger RL, Roberts AL, Vale WW, Geyer MA (2004) Corticotropin-releasing factor receptors CRF1 and CRF2 exert both additive and opposing influences on defensive startle behavior. J Neurosci 24:6545–6552

    Article  CAS  PubMed  Google Scholar 

  • Rosener B (2006) Hypothesis testing: one-sample inference. in book hypothesis testing: one-sample inference. The Thompson Corporation, Belmont p 234

  • Spina M, Merlo-Pich E, Chan RK, Basso AM, Rivier J, Vale W, Koob GF (1996) Appetite-suppressing effects of urocortin, a CRF-related neuropeptide. Science 273:1561–1564

    Article  CAS  PubMed  Google Scholar 

  • Spina MG, Merlo-Pich E, Akwa Y, Balducci C, Basso M, Zorrilla P, Britton T, Rivier J, Vale W, Koob F (2002) Time-dependent induction of anxiogenic-like effects after central infusion of urocortin or corticotropin-releasing factor in the rat. Psychopharmacology (Berl) 160:113–121

    Article  CAS  Google Scholar 

  • Spina MG, Langnaese K, Orlando GF, Horn TF, Rivier J, Vale WW, Wolf G, Engelmann M (2004) Colocalization of urocortin and neuronal nitric oxide synthase in the hypothalamus and Edinger–Westphal nucleus of the rat. J Comp Neurol 479:271–286

    Article  CAS  PubMed  Google Scholar 

  • Swinny JD, Kalicharan D, Gramsbergen A, van der Want JJ (2002) The localisation of urocortin in the adult rat cerebellum: a light and electron microscopic study. Neuroscience 114:891–903

    CAS  PubMed  Google Scholar 

  • Valdez GR, Zorrilla EP, Rivier J, Vale WW, Koob GF (2003) Locomotor suppressive and anxiolytic-like effects of urocortin 3, a highly selective type 2 corticotropin-releasing factor agonist. Brain Res 980:206–212

    Article  CAS  PubMed  Google Scholar 

  • van Erp AM, Kruk MR, Willekens-Bramer DC, Fermont PC, Nijsen MJ (1995) PVH lesions do not inhibit stressor-induced grooming in the rat. Physiol Behav 57:887–892

    Article  PubMed  Google Scholar 

  • Van Pett K, Viau V, Bittencourt JC, Chan RK, Li HY, Arias C, Prins GS, Perrin M, Vale W, Sawchenko PE (2000) Distribution of mRNAs encoding CRF receptors in brain and pituitary of rat and mouse. J Comp Neurol 428:191–212

    Article  PubMed  Google Scholar 

  • Vaughan J, Donaldson C, Bittencourt J, Perrin MH, Lewis K, Sutton S, Chan R, Turnbull AV, Lovejoy D, Rivier C, Rivier J, Sawchenko PE, Vale W (1995) Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor. Nature 378:287–292

    Article  CAS  PubMed  Google Scholar 

  • Wotjak CT, Ludwig M, Ebner K, Russell JA, Singewald N, Landgraf R, Engelmann M (2002) Vasopressin from hypothalamic magnocellular neurons has opposite actions at the adenohypophysis and in the supraoptic nucleus on ACTH secretion. Eur J Neurosci 16:477–485

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Rita Murau and Imgard Leschka for excellent technical assistance. The study was supported by DFG (EN 366/6-1, 436 UNG 113/168/0-2 and SP 672/1-3).

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Correspondence to Mario Engelmann.

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Fatima, A., Haroon, M.F., Wolf, G. et al. Urocortin 1 administered into the hypothalamic supraoptic nucleus affects open-field behaviour in rats. Amino Acids 38, 1407–1414 (2010). https://doi.org/10.1007/s00726-009-0349-1

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  • DOI: https://doi.org/10.1007/s00726-009-0349-1

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