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α2-adrenoceptor binding in Flinders-sensitive line compared with Flinders-resistant line and Sprague-Dawley rats

Published online by Cambridge University Press:  23 April 2015

Thea Pinholt Lillethorup ,
Peter Iversen ,
Gregers Wegener ,
Doris Jeanne Marie Doudet  and
Anne Marlene Landau
Thea Pinholt Lillethorup
Affiliation:
Department of Nuclear Medicine and PET Center, Aarhus University, Denmark Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark
Peter Iversen
Affiliation:
Department of Nuclear Medicine and PET Center, Aarhus University, Denmark
Gregers Wegener
Affiliation:
Center for Psychiatric Research, Aarhus University, Denmark Centre for Pharmaceutical Excellence, School of Pharmacy (Pharmacology), North-West University, Potchefstroom, South Africa
Doris Jeanne Marie Doudet
Affiliation:
Department of Nuclear Medicine and PET Center, Aarhus University, Denmark Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark Department of Medicine/Neurology, University of British Columbia, Canada
Anne Marlene Landau*
Affiliation:
Department of Nuclear Medicine and PET Center, Aarhus University, Denmark Center of Functionally Integrative Neuroscience/MINDlab, Aarhus University, Denmark
*
Dr. Anne M. Landau, Department of Nuclear Medicine and PET Center, Aarhus University, Nørrebrogade 44, Building 10G, 8000Aarhus C, Denmark. Tel: +457 846 4378; Fax: +457 846 1662; E-mail: [email protected]
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Abstract

Objectives

Disturbances in the noradrenergic system, including alterations in the densities of α2-adrenoceptors, are posited to be involved in the pathophysiology of depression. In this study, we investigate the binding of α2-adrenoceptors in regions relevant to depression in an animal model of depression.

Methods

Using in vitro autoradiography techniques and the selective α2-ligand, [3H]RX 821002, we investigated the density of α2-adrenoceptors in female Flinders-sensitive line (FSL) rats, a validated model of depression, and in two traditional control groups – female Flinders-resistant line (FRL) and Sprague-Dawley (SD) rats.

Results

The α2-adrenoceptor density was increased in most regions of the FSL rat brain when compared with SD rats (10% across regions). Moreover, the α2-adrenoceptor density was further increased in the FRL rats compared with both FSL (10% across regions) and SD rats (24% across regions).

Conclusions

The increase in α2-adrenoceptor binding in cortical regions in the FSL strain compared with the SD control strain is in accord with α2-adrenoceptor post-mortem binding data in suicide victims with untreated major depression. However, the differences in binding observed in the two control groups were unexpected and suggest the need for further studies in a larger cohort of animals of both sexes.

Keywords

adrenergic alpha-2 receptorautoradiographydepressionFlinders-resistant line ratsFlinders-sensitive line rats
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 6 , December 2015 , pp. 345 - 352
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Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

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References

1. WHO. The Global Burden of Disease: 2004 Update. Geneva, Switzerland: WHO, 2008.Google Scholar
2. Marcus, M, Yasamy, MT, van Ommeren, M, Chrisholm, D, Saxena, S. Depression: A Global Public Health Concern: WHO Department of Mental Health and Substance Abuse. Geneva, Switzerland: WHO, 2012.Google Scholar
3. Schildkraut, JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry 1965;122:509–522.CrossRefGoogle ScholarPubMed
4. Drevets, WC. Neuroimaging studies of mood disorders. Biol Psychiatry 2000;48:813–829.Google Scholar
5. Overstreet, DH, Russell, RW, Helps, SC, Messenger, M. Selective breeding for sensitivity to the anticholinesterase DFP. Psychopharmacology 1979;65:15–20.CrossRefGoogle Scholar
6. Overstreet, DH, Russell, RW. Selective breeding for diisopropyl fluorophosphate-sensitivity: behavioural effects of cholinergic agonists and antagonists. Psychopharmacology 1982;78:150–155.Google Scholar
7. Wegener, G, Mathe, AA, Neumann, ID. Selectively bred rodents as models of depression and anxiety. Curr Top Behav Neurosci 2012;12:139–187.CrossRefGoogle ScholarPubMed
8. Janowsky, DS, Overstreet, DH, Nurnberger, JI Jr. Is cholinergic sensitivity a genetic marker for the affective disorders? Am J Med Genet 1994;54:335–344.CrossRefGoogle ScholarPubMed
9. Pucilowski, O, Overstreet, DH, Rezvani, AH, Janowsky, DS. Chronic mild stress-induced anhedonia: greater effect in a genetic rat model of depression. Physiol Behav 1993;54:1215–1220.CrossRefGoogle Scholar
10. Overstreet, DH, Friedman, E, Mathe, AA, Yadid, G. The Flinders sensitive line rat: a selectively bred putative animal model of depression. Neurosci Biobehav Rev 2005;29:739–759.CrossRefGoogle Scholar
11. Matthews, K, Baldo, BA, Markou, A, Lown, O, Overstreet, DH, Koob, GF. Rewarding electrical brain stimulation: similar thresholds for Flinders sensitive line hypercholinergic and Flinders resistant line hypocholinergic rats. Physiol Behav 1996;59:1155–1162.Google Scholar
12. Overstreet, DH, Wegener, G. The Flinders sensitive line rat model of depression–25 years and still producing. Pharmacol Rev 2013;65:143–155.Google Scholar
13. Overstreet, DH, Keeney, A, Hogg, S. Antidepressant effects of citalopram and CRF receptor antagonist CP-154,526 in a rat model of depression. Eur J Pharmacol 2004;492:195–201.CrossRefGoogle Scholar
14. Chen, F, Madsen, TM, Wegener, G, Nyengaard, JR. Imipramine treatment increases the number of hippocampal synapses and neurons in a genetic animal model of depression. Hippocampus 2010;20:1376–1384.CrossRefGoogle Scholar
15. Meana, JJ, Garcia-Sevilla, JA. Increased alpha 2-adrenoceptor density in the frontal cortex of depressed suicide victims. J Neural Transm 1987;70:377–381.Google Scholar
16. De Paermentier, F, Mauger, JM, Lowther, S, Crompton, MR, Katona, CL, Horton, RW. Brain alpha-adrenoceptors in depressed suicides. Brain Res 1997;757:60–68.Google Scholar
17. Gonzalez, AM, Pascual, J, Meana, JJ et al. Autoradiographic demonstration of increased alpha 2-adrenoceptor agonist binding sites in the hippocampus and frontal cortex of depressed suicide victims. J Neurochem 1994;63:256–265.Google Scholar
18. Ordway, GA, Widdowson, PS, Smith, KS, Halaris, A. Agonist binding to alpha 2-adrenoceptors is elevated in the locus coeruleus from victims of suicide. J Neurochem 1994;63(2):617–624.Google Scholar
19. Subhash, MN, Nagaraja, MR, Sharada, S, Vinod, KY. Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain. Neurochem Int 2003;43:603–609.CrossRefGoogle ScholarPubMed
20. Arango, V, Ernsberger, P, Sved, AF, Mann, JJ. Quantitative autoradiography of alpha 1- and alpha 2-adrenergic receptors in the cerebral cortex of controls and suicide victims. Brain Res 1993;630:271–282.CrossRefGoogle ScholarPubMed
21. Klimek, V, Rajkowska, G, Luker, SN et al. Brain noradrenergic receptors in major depression and schizophrenia. Neuropsychopharmacology 1999;21:69–81.Google Scholar
22. Langer, SZ. Presynaptic regulation of catecholamine release. Biochem Pharmacol 1974;23:1793–1800.CrossRefGoogle ScholarPubMed
23. Frankhuyzen, AL, Mulder, AH. Pharmacological characterization of presynaptic alpha-adrenoceptors modulating [3H]noradrenaline and [3H]5-hydroxytryptamine release from slices of the hippocampus of the rat. Eur J Pharmacol 1982;81:97–106.Google Scholar
24. Gresch, PJ, Sved, AF, Zigmond, MJ, Finlay, JM. Local influence of endogenous norepinephrine on extracellular dopamine in rat medial prefrontal cortex. J Neurochem 1995;65:111–116.Google Scholar
25. Arnsten, AF, Scahill, L, Findling, RL. alpha2-Adrenergic receptor agonists for the treatment of attention-deficit/hyperactivity disorder: emerging concepts from new data. J Child Adolesc Psychopharmacol 2007;17:393–406.CrossRefGoogle ScholarPubMed
26. Lillethorup, TP, Iversen, P, Fontain, J, Wegener, G, Doudet, DJ, Landau, AM. Electroconvulsive shocks decrease α2-adrenoceptor binding in the Flinders rat model of depression. Eur Neuropsychopharmacol 2015;25:404–412.CrossRefGoogle ScholarPubMed
27. Paxinos, G, Watson, C. The Rat Brain in Stereotaxic Coordinates, 4th edn. San Diego: Academic Press, 1998.Google Scholar
28. Booze, RM, Wallace, DR, Silvers, JM, Strupp, BJ, Snow, DM, Mactutus, CF. Prenatal cocaine exposure alters alpha2 receptor expression in adolescent rats. BMC Neurosci 2006;7:33.CrossRefGoogle ScholarPubMed
29. R Core Team. R: A Language and Environment for Statistical Computing. Version 3.1.0. Vienna, Austria: R Foundation for Statistical Computing. http://www.R-project.org 2014.Google Scholar
30. Meana, JJ, Barturen, F, Garcia-Sevilla, JA. Alpha 2-adrenoceptors in the brain of suicide victims: increased receptor density associated with major depression. Biol Psychiatry 1992;31:471–490.CrossRefGoogle ScholarPubMed
31. Willner, P, Scheel-Kruger, J, Belzung, C. The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 2013;37:2331–2371.Google Scholar
32. Murray, EA, Bussey, TJ, Saksida, LM. Visual perception and memory: a new view of medial temporal lobe function in primates and rodents. Ann Rev Neurosci 2007;30:99–122.CrossRefGoogle ScholarPubMed
33. Beneyto, M, Kristiansen, LV, Oni-Orisan, A, McCullumsmith, RE, Meador-Woodruff, JH. Abnormal glutamate receptor expression in the medial temporal lobe in schizophrenia and mood disorders. Neuropsychopharmacology 2007;32:1888–1902.CrossRefGoogle ScholarPubMed
34. Scoville, WB, Milner, B. Loss of recent memory after bilateral hippocampal lesions. 1957. J Neuropsychiatry Clin Neurosci 2000;12:103–113.CrossRefGoogle ScholarPubMed
35. Belzung, C, Billette de Villemeur, E. The design of new antidepressants: can formal models help? A first attempt using a model of the hippocampal control over the HPA-axis based on a review from the literature. Behav Pharmacol 2010;21:677–689.CrossRefGoogle Scholar
36. Jacobson, L, Sapolsky, R. The role of the hippocampus in feedback regulation of the hypothalamic-pituitary-adrenocortical axis. Endocr Rev 1991;12:118–134.CrossRefGoogle ScholarPubMed
37. van Groen, T, Kadish, I, Wyss, JM. The role of the laterodorsal nucleus of the thalamus in spatial learning and memory in the rat. Behav Brain Res 2002;136:329–337.CrossRefGoogle ScholarPubMed
38. Quan, M, Zheng, C, Zhang, N et al. Impairments of behavior, information flow between thalamus and cortex, and prefrontal cortical synaptic plasticity in an animal model of depression. Brain Res Bull 2011;85:109–116.Google Scholar
39. Young, KA, Holcomb, LA, Yazdani, U, Hicks, PB, German, DC. Elevated neuron number in the limbic thalamus in major depression. Am J Psychiatry 2004;161:1270–1277.CrossRefGoogle ScholarPubMed
40. Overstreet, DH, Russell, RW, Crocker, AD, Schiller, GD. Selective breeding for differences in cholinergic function: pre- and postsynaptic mechanisms involved in sensitivity to the anticholinesterase, DFP. Brain Res 1984;294:327–332.Google Scholar
41. Hasegawa, S, Nishi, K, Watanabe, A, Overstreet, DH, Diksic, M. Brain 5-HT synthesis in the Flinders sensitive line rat model of depression: an autoradiographic study. Neurochem Int 2006;48:358–366.Google Scholar
42. Kanemaru, K, Nishi, K, Hasegawa, S, Diksic, M. Chronic citalopram treatment elevates serotonin synthesis in Flinders sensitive and Flinders resistant lines of rats, with no significant effect on Sprague-Dawley rats. Neurochem Int 2009;54:363–371.CrossRefGoogle ScholarPubMed
43. Kovacevic, T, Skelin, I, Minuzzi, L, Rosa-Neto, P, Diksic, M. Reduced metabotropic glutamate receptor 5 in the Flinders sensitive line of rats, an animal model of depression: an autoradiographic study. Brain Res Bull 2012;87:406–412.CrossRefGoogle ScholarPubMed
44. Wegener, G, Harvey, BH, Bonefeld, B et al. Increased stress-evoked nitric oxide signalling in the Flinders sensitive line (FSL) rat: a genetic animal model of depression. Int J Neuropsychopharmacol 2010;13:461–473.CrossRefGoogle Scholar