Antagonism of CRF 2 receptors produces anxiolytic behavior in animal models of anxiety

Antagonism of CRF 2 receptors produces anxiolytic behavior in animal models of anxiety Two pharmacologically distinct CRF receptors are distributed in different brain regions and peripheral tissues. Studies suggest that CRF 1 receptors play an important role in mediating the anxiety provoking effects of CRF. In contrast, far less functional information is available on CRF 2 receptors. Therefore, we conducted dose response studies using antisauvagine-30 (anti-SVG-30, 0–20 μg, 20-min pretreatment, i.c.v.), a potent CRF 2 peptide antagonist, and tested rats in three models of anxiety — the conditioned freezing, the elevated plus maze, and the defensive-withdrawal test. Anti-SVG-30 produced a significant dose-dependent reduction in conditioned freezing. In the elevated plus maze test, administration of anti-SVG-30 effectively increased the number of entries and time spent in the open arms. In the defensive-withdrawal test, anti-SVG-30 treatment facilitated exploratory activity in a large illuminated open field. Thus, in all three animal models, administration of anti-SVG-30 was consistent in producing an anxiolytic-like behavioral effect. In addition, a dose of anti-SVG-30 (10 μg) that produced anxiolytic-like behavior had no significant effects on locomotor activity measured in an automated activity box. This latter finding suggests that antagonism of CRF 2 receptors is not associated with a non-specific increase in behavioral movements. These results provide evidence that, in addition to CRF 1 receptors, CRF 2 receptors may play an important role in the mediation of anxiety behavior. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Antagonism of CRF 2 receptors produces anxiolytic behavior in animal models of anxiety

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Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0006-8993
DOI
10.1016/S0006-8993(01)02405-2
Publisher site
See Article on Publisher Site

Abstract

Two pharmacologically distinct CRF receptors are distributed in different brain regions and peripheral tissues. Studies suggest that CRF 1 receptors play an important role in mediating the anxiety provoking effects of CRF. In contrast, far less functional information is available on CRF 2 receptors. Therefore, we conducted dose response studies using antisauvagine-30 (anti-SVG-30, 0–20 μg, 20-min pretreatment, i.c.v.), a potent CRF 2 peptide antagonist, and tested rats in three models of anxiety — the conditioned freezing, the elevated plus maze, and the defensive-withdrawal test. Anti-SVG-30 produced a significant dose-dependent reduction in conditioned freezing. In the elevated plus maze test, administration of anti-SVG-30 effectively increased the number of entries and time spent in the open arms. In the defensive-withdrawal test, anti-SVG-30 treatment facilitated exploratory activity in a large illuminated open field. Thus, in all three animal models, administration of anti-SVG-30 was consistent in producing an anxiolytic-like behavioral effect. In addition, a dose of anti-SVG-30 (10 μg) that produced anxiolytic-like behavior had no significant effects on locomotor activity measured in an automated activity box. This latter finding suggests that antagonism of CRF 2 receptors is not associated with a non-specific increase in behavioral movements. These results provide evidence that, in addition to CRF 1 receptors, CRF 2 receptors may play an important role in the mediation of anxiety behavior.

Journal

Brain ResearchElsevier

Published: Jun 1, 2001

References

  • Neuroanatomical characterization of Fos induction in rat behavioral models of anxiety
    Duncan, G.E; Knapp, D.J; Breese, G.R
  • The discovery of 4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-(1,5- a )-pyrimidine: a corticotropin-releasing factor (hCRF 1 ) antagonist
    Gilligan, P.J; Baldauf, C; Cocuzza, A; Chidester, D; Zaczek, R; Fitzgerald, L.W; McElroy, J; Smith, M.A; Shen, H.-S.L; Saye, J.A; Christ, D; Trainor, G; Robertson, D.W; Hartig, P
  • Characterization of the behavioral profile of the non-peptide CRF receptor antagonist CP-154,526 in anxiety models in rodents
    Griebel, G; Perrault, G; Sanger, D.J
  • Corticotropin-releasing factor CRF 1 , but not CRF 2 , receptors mediate anxiogenic-like behavior
    Heinrichs, S.C; Lapsansky, J; Lovenberg, T.W; De Souza, E.B; Chalmers, D.T
  • 125 I-antisauvagine-30: a novel and specific high-affinity radioligand for the characterization of corticotropin-releasing factor type 2 receptors
    Higelin, J; Py-Lang, G; Paternoser, C; Ellis, G.J; Patel, A; Dautzenberg, F.M
  • The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety
    Holsboer, F
  • Differential behavioural effects of chronic infusion of CRH 1 and CRH 2 receptor antisense oligonucleotides into the rat brain
    Liebsch, G; Landgraf, R; Engelmann, M; Lörscher, P; Holsober, F
  • A non-peptidic corticotropin releasing factor receptor antagonist attenuates fever and exhibits anxiolytic-like activity
    Lundkvist, J; Chai, Z; Teheranian, R; Hasanvan, H; Bartfai, T; Jenck, F; Widmer, U; Moreau, J.-L
  • Corticosterone delivery to the amygdala increases corticotropin-releasing factor mRNA in the central amygdaloid nucleus and anxiety-like behavior
    Shepard, J.D; Barron, K.W; Myers, D.A

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