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Psychopharmacology (Berl). 2001 Jul;156(2-3):284-90.

The DBA/2J strain and prepulse inhibition of startle: a model system to test antipsychotics?

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1
PsychoGenics Inc., Hawthorne, NY 10532, USA. b.olivier@pharm.uu.nl

Abstract

RATIONALE:

Prepulse inhibition (PPI) of the startle response in mice is increasingly used as a paradigm of sensory gating with potential predictive and construct validity towards schizophrenia.

OBJECTIVES:

Establishment of a mouse PPI paradigm in which typical and atypical antipsychotic drugs directly improve a low performance PPI.

METHODS:

Three strains of mice--C57Bl/6J, 129S6/SvEvTac and DBA/2J--were tested in a startle paradigm with three prepulse intensities, 2, 4 and 8 dB above background.

RESULTS:

Under these conditions, risperidone (0, 0.25, 0.5 and 1 mg/kg i.p.) and clozapine (0, 1, 3 and 9 mg/kg i.p.) improved PPI in all three strains, with order of effect in DBA/2J > 129S6SvEvTac > C57Bl/6J. The DBA/2J strain showed larger PPI-enhancing effects, without disturbing the basal startle response. Two alpha7 nicotinic receptor agonists, GTS-21 (1-10 mg/kg i.p.) and AR-R17779 (1-10 mg/kg i.p.) were inactive in the PPI procedure in DBA/2J mice.

CONCLUSIONS:

DBA/2J mice were very sensitive to the antipsychotic-like effects of atypical (clozapine) and typical (risperidone) antipsychotics, and this strain is proposed as a model to directly measure sensory gating properties of drugs. Alpha7 Nicotinergic receptor agonists were ineffective in this PPI paradigm.

PMID:
11549230
[Indexed for MEDLINE]
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