Atypical antipsychotics clozapine and quetiapine attenuate prepulse inhibition deficits in dopamine transporter knockout mice.
Sensorimotor gating disruptions are seen in various psychiatric illnesses with putatively different pathologies, including schizophrenia and bipolar disorder. Interestingly, mice lacking the dopamine (DA) transporter (DAT) gene display markedly increased levels of DA, deficits in sensorimotor gating, and hyperactivity relative to wild-type mice. Atypical antipsychotics are effective treatments of schizophrenia and manic symptoms, presumably in part by antagonizing DA receptors. Here we report that treatment with clozapine (3 mg/kg) or quetiapine (2.5 mg/kg) attenuated prepulse inhibition deficits in male DAT knockout mice. Thus male DAT knockout mice may provide a useful animal model for predicting the efficacy of novel drugs in treating psychiatric illnesses characterized by a dysregulated DA system.
Powell
Susan B
SB
aDepartment of Psychiatry, University of California, San Diego, La Jolla, California 92093-0804, USA. sbpowell@ucsd.edu
Young
Jared W
JW
Ong
Jacob C
JC
Caron
Marc G
MG
Geyer
Mark A
MA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D007274:Injections, Intraperitoneal; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D000069348:Quetiapine Fumarate; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D050483:Dopamine Plasma Membrane Transport Proteins; D000069348:Quetiapine Fumarate; D003024:Clozapine