Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor

Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor The main biological role of angiotensin II type 2 receptor (AT 2 ) has not been established. We made use of targeted disruption of the mouse AT 2 gene to examine the role of the AT 2 receptor in the central nervous system (CNS). AT 2 -deficient mice displayed anxiety-like behavior compared with wild-type mice. However, AT 2 -deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice. Both noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I converting enzyme inhibitor), prazosin (α 1 antagonist) reversed the anxiety-like behavior in these AT 2 -deficient mice, whereas yohimbine (α 2 antagonist), phenylephrine (α 1 agonist), clonidine (α 2 agonist), isoproterenol (β 1 /β 2 agonist), propranolol (β 1 /β 2 antagonist) and α-helical CRF 9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like behavior in AT 2 -deficient mice. In addition, concentrations of plasma adrenocorticotropic hormone (ACTH) and corticosterone in AT 2 -deficient mice did not differ from these in wild-type mice, hence, there are probably no endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The amygdala appears to play an important role in many of the responses to fear and anxiety. The number of ( 3 H )prazosin but not ( 125 I )CRF binding sites in the amygdala was significantly reduced in AT 2 -deficient mice. These findings indicate that the noradrenergic system is involved in mediating the anxiety-like behavior in AT 2 -deficient mice. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Anxiety-like behavior in mice lacking the angiotensin II type-2 receptor

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Publisher
Elsevier
Copyright
Copyright © 1999 Elsevier Science B.V.
ISSN
0006-8993
DOI
10.1016/S0006-8993(99)01098-7
Publisher site
See Article on Publisher Site

Abstract

The main biological role of angiotensin II type 2 receptor (AT 2 ) has not been established. We made use of targeted disruption of the mouse AT 2 gene to examine the role of the AT 2 receptor in the central nervous system (CNS). AT 2 -deficient mice displayed anxiety-like behavior compared with wild-type mice. However, AT 2 -deficient mice showed no depressant-like activity and no change in hexobarbital-induced sleeping time as compared with findings in wild-type mice. Both noradrenergic and corticotropin-releasing factor (CRF) neuronal systems appear to be involved in this anxiety-like behavior. Diazepam, captopril (angiotensin I converting enzyme inhibitor), prazosin (α 1 antagonist) reversed the anxiety-like behavior in these AT 2 -deficient mice, whereas yohimbine (α 2 antagonist), phenylephrine (α 1 agonist), clonidine (α 2 agonist), isoproterenol (β 1 /β 2 agonist), propranolol (β 1 /β 2 antagonist) and α-helical CRF 9-41 (CRF receptor antagonist) has no apparent effects on anxiety-like behavior in AT 2 -deficient mice. In addition, concentrations of plasma adrenocorticotropic hormone (ACTH) and corticosterone in AT 2 -deficient mice did not differ from these in wild-type mice, hence, there are probably no endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis (HPA). The amygdala appears to play an important role in many of the responses to fear and anxiety. The number of ( 3 H )prazosin but not ( 125 I )CRF binding sites in the amygdala was significantly reduced in AT 2 -deficient mice. These findings indicate that the noradrenergic system is involved in mediating the anxiety-like behavior in AT 2 -deficient mice.

Journal

Brain ResearchElsevier

Published: Mar 6, 1999

References

  • Angiotensin II receptor subtypes in mouse brain
    Häuser, W.; Jöhren, O.; Sanvitto, G.L.; Inagami, T.; Saavedra, J.M.
  • Angiotensin AT 1 receptor-mediated vasopressin release and drinking are potentiated by an AT 2 receptor antagonist
    Hohle, S.; Spitznagel, H.; Rascher, W.; Culman, J.; Unger, T.
  • Localization of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor subtypes, and vasopressin in the mouse hypothalamus
    Jöhren, O.; Imboden, H.; Häuser, W.; Maye, I.; Sanvitto, G.L.; Saavedra, J.M.
  • The use of a plus-maze to measure anxiety in the mouse
    Lister, R.G.
  • Physiological actions of angiotensin II mediated by AT 1 and AT 2 receptors in the brain
    McKinley, M.J.; McAllen, R.M.; Pennington, G.L.; Smardencas, A.; Weisinger, R.S.; Oldfield, B.J.
  • Regulation of angiotensin II binding sites in neuronal cultures by catecholamines
    Myers, L.M.; Sumners, C.
  • Behavioral evidence for modulation by sigma ligands of (+)MK-801-induced hyperlocomotion in monoamine-depleted mice
    Okuyama, S.; Imagawa, Y.; Tomisawa, K.
  • Behaviour of the transgenic (mREN2)27 rat
    Wilson, W.; Voigt, P.; Bader, M.; Marsden, C.A.; Fink, H.

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