Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4332969 | Brain Research | 2006 | 9 Pages |
Abstract
Genetically altered mice with reductions in the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor have been proposed as a model for the intrinsic NMDA hypofunction hypothesized for schizophrenia. The following study investigated whether NR1-deficient mice have enhanced susceptibility for the effects of amphetamine, similar to the exaggerated responsivity to dopamine agonists observed in many schizophrenia patients. NR1â/â mice and wild-type controls were tested for the effects of amphetamine (2-10Â mg/kg) on prepulse inhibition of acoustic startle responses. The results showed that mice with reduced NMDA receptor function demonstrated consistent deficits in prepulse inhibition (PPI), as well as higher startle response amplitudes. In comparison to normal controls, the NR1â/â mice were more sensitive to the disruptive effects of amphetamine on PPI, but not to the drug effects on startle magnitude without a prepulse stimulus. Wild-type mice only showed decreased PPI at the highest dose of amphetamine tested (10Â mg/kg) and demonstrated small increases in PPI at lower amphetamine doses (2 and 6Â mg/kg). The NR1â/â mice did not show enhanced PPI in response to amphetamine at low doses, with reductions in PPI apparent at doses of 4-10Â mg/kg. Overall, these findings suggest that the NR1â/â mouse may provide a model for enhanced sensitivity to dopamine agonist-induced disruption of PPI.
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Authors
Sheryl S. Moy, Antonio Perez, Beverly H. Koller, Gary E. Duncan,