The dopamine D2 agonist quinpirole impairs frontal mismatch responses to sound frequency deviations in freely moving rats

Abstract

Aim: A reduced mismatch negativity (MMN) response is a promising electrophysiological endophenotype of schizophrenia that reflects neurocognitive impairment. Dopamine dysfunction is associated with symptoms of schizophrenia. However, whether the dopamine system is involved in MMN impairment remains controversial. In this study, we investigated the effects of the dopamine D2-like receptor agonist quinpirole on mismatch responses to sound frequency changes in an animal model. Methods: Event-related potentials were recorded from electrocorticogram electrodes placed on the auditory and frontal cortices of freely moving rats using a frequency oddball paradigm consisting of ascending and equiprobable (ie, many standards) control sequences before and after the subcutaneous administration of quinpirole. To detect mismatch responses, difference waveforms were obtained by subtracting nondeviant control waveforms from deviant waveforms. Results: Here, we show the significant effects of quinpirole on frontal mismatch responses to sound frequency deviations in rats. Quinpirole delayed the frontal N18 and P30 mismatch responses and reduced the frontal N55 MMN-like response, which resulted from the reduction in the N55 amplitude to deviant stimuli. Importantly, the magnitude of the N55 amplitude was negatively correlated with the time of the P30 latency in the difference waveforms. In contrast, quinpirole administration did not clearly affect the temporal mismatch responses recorded from the auditory cortex. Conclusion: These results suggest that the disruption of dopamine D2-like receptor signaling by quinpirole reduces frontal MMN to sound frequency deviations and that delays in early mismatch responses are involved in this MMN impairment.