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Anxiogenic treatments do not increase fear-potentiated startle in mice.
Biol Psychiatry. 2005 Jan 01; 57(1):33-43.BP

Abstract

BACKGROUND

In rodents, the fear-potentiated startle paradigm (FPS; exaggerated startle as a measure of the conditioned fear response to cues associated with footshock) has demonstrated predictive validity for anxiolytic drugs. The predictive validity of the model for anxiogenic drugs, however, remains unclear. Therefore, we evaluated the bi-directionality of the FPS model for anxiety-modulating compounds in mice.

METHODS

The clinical anxiogenics FG-7142 (1-20 mg/kg), yohimbine (.1-10 mg/kg), and m-Chlorophenylpiperazine (mCPP; .3-3 mg/kg), and the putative anxiogenics atipamezole (.3-3 mg/kg) and corticotropin-releasing factor (h/r-CRF; .03-1 microg) were tested in DBA/1J mice trained for FPS.

RESULTS

Contrary to predictions, FG-7142 (10 and 20 mg/kg) and yohimbine (10 mg/kg) reduced FPS in mice without affecting baseline startle. Atipamezole (3 mg/kg), mCPP (3 mg/kg), and h/r-CRF (.3, 1 microg) did not affect FPS, but increased startle independently from the presence of the cue. FG-7142 and h/r-CRF had similar effects in 129SvEv mice.

CONCLUSIONS

Murine FPS is not bi-directionally predictive for anxiety-modulating compounds, although murine baseline startle may have some utility as a bi-directional model of anxiety. These data corroborate the recent hypothesis that systems mediating FPS are independent from systems mediating increased startle from unconditioned and putatively anxiogenic stimuli.

Authors+Show Affiliations

Departments of Psychiatry and Neurosciences, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0804, USA.No affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15607298

Citation

Risbrough, Victoria B., and Mark A. Geyer. "Anxiogenic Treatments Do Not Increase Fear-potentiated Startle in Mice." Biological Psychiatry, vol. 57, no. 1, 2005, pp. 33-43.
Risbrough VB, Geyer MA. Anxiogenic treatments do not increase fear-potentiated startle in mice. Biol Psychiatry. 2005;57(1):33-43.
Risbrough, V. B., & Geyer, M. A. (2005). Anxiogenic treatments do not increase fear-potentiated startle in mice. Biological Psychiatry, 57(1), 33-43.
Risbrough VB, Geyer MA. Anxiogenic Treatments Do Not Increase Fear-potentiated Startle in Mice. Biol Psychiatry. 2005 Jan 1;57(1):33-43. PubMed PMID: 15607298.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anxiogenic treatments do not increase fear-potentiated startle in mice. AU - Risbrough,Victoria B, AU - Geyer,Mark A, PY - 2004/04/23/received PY - 2004/08/09/revised PY - 2004/10/20/accepted PY - 2004/12/21/pubmed PY - 2005/3/15/medline PY - 2004/12/21/entrez SP - 33 EP - 43 JF - Biological psychiatry JO - Biol Psychiatry VL - 57 IS - 1 N2 - BACKGROUND: In rodents, the fear-potentiated startle paradigm (FPS; exaggerated startle as a measure of the conditioned fear response to cues associated with footshock) has demonstrated predictive validity for anxiolytic drugs. The predictive validity of the model for anxiogenic drugs, however, remains unclear. Therefore, we evaluated the bi-directionality of the FPS model for anxiety-modulating compounds in mice. METHODS: The clinical anxiogenics FG-7142 (1-20 mg/kg), yohimbine (.1-10 mg/kg), and m-Chlorophenylpiperazine (mCPP; .3-3 mg/kg), and the putative anxiogenics atipamezole (.3-3 mg/kg) and corticotropin-releasing factor (h/r-CRF; .03-1 microg) were tested in DBA/1J mice trained for FPS. RESULTS: Contrary to predictions, FG-7142 (10 and 20 mg/kg) and yohimbine (10 mg/kg) reduced FPS in mice without affecting baseline startle. Atipamezole (3 mg/kg), mCPP (3 mg/kg), and h/r-CRF (.3, 1 microg) did not affect FPS, but increased startle independently from the presence of the cue. FG-7142 and h/r-CRF had similar effects in 129SvEv mice. CONCLUSIONS: Murine FPS is not bi-directionally predictive for anxiety-modulating compounds, although murine baseline startle may have some utility as a bi-directional model of anxiety. These data corroborate the recent hypothesis that systems mediating FPS are independent from systems mediating increased startle from unconditioned and putatively anxiogenic stimuli. SN - 0006-3223 UR - https://www.unboundmedicine.com/medline/citation/15607298/Anxiogenic_treatments_do_not_increase_fear_potentiated_startle_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(04)01069-8 DB - PRIME DP - Unbound Medicine ER -