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


OBJECTIVE
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.
Olivier
B
B
PsychoGenics Inc., Hawthorne, NY 10532, USA. b.olivier@pharm.uu.nl
Leahy
C
C
Mullen
T
T
Paylor
R
R
Groppi
V E
VE
Sarnyai
Z
Z
Brunner
D
D
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008960:Models, Psychological; D018722:Nicotinic Agonists / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects*; D018967:Risperidone / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor
C408128:AR-R 17779; D014150:Antipsychotic Agents; D001597:Benzylidene Compounds; D001952:Bridged-Ring Compounds; C579166:Chrna7 protein, mouse; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D013141:Spiro Compounds; D064569:alpha7 Nicotinic Acetylcholine Receptor; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D003024:Clozapine; D018967:Risperidone