Effect of dopamine D1 receptor antagonist SCH23390 on electrophysiological activity of entopeduncular nuclei in parkinsonian rats

Objective To study the effect of dopamine D1 receptor antagonist SCH23390 on the behavior of parkinsonian (PD) rats and on electrophysiological characteristics of the entopeduncular nucleus (EP). Methods Intracranial injection of 6-OHDA was conducted in 23 adult male Wistar rats to create PD animal models (experimental group) while the same amount of normal saline was injected in another 19 rats as a control group. (1) After intraperitoneal injection of SCH23390 at various concentrations of 0.010, 0.015, 0.020, 0.025 and 0.030 mg/kg, the step frequency and the discontinuous moving frequency tests were carried out to determine the optimal concentration and time of intervention at 6 time points (10 min before, and 5~15, 20~30, 30~40, 40~50 and 68~78 min after intervention) when all the rats were put on a treadmill at a speed of 8 r/min. (2) After recording electrodes were implanted into the EP in the rats, the signals of spikes in the EP in still and movement conditions were recorded simultaneously using the 16-Channel OmniPlex Neural Data Acquisition System. The spike signals collected were imported into Offline Sorter to do cluster-sorting analysis and then into NeuroExplorer to analyze alterations in the firing pattern and firing rate of each type of neuron. (3) Frozen sections of the brain samples harvested by perfusion from the rats in the 2 groups were subjected to Nissl's staining and histological assay. Results (1) The behavioral tests showed that intraperitoneal injection of SCH23390 at 0.020 mg/kg at time points of 20~30 min and 30~40 min was optimal. The step frequency for the experimental group (24.47±1.35 step/min) was significantly decreased compared with that for the control group (30.77 ± 2.06 step/min) (t=7.392, P=0.000). (2) After intervention by SCH23390, in movement and still conditions, the firing rate and variation coefficient of EP neurons were significantly higher in the experimental group than in the control group (P<0.05). (3) The Nissl's staining showed a small number of lightly stained neurons were sparsely disposed in the injured cerebral substantia nigra and the histological assay found altogether 14 rats from which correct EP sites were collected. Conclusions This study demonstrated a negative regulating effect of dopamine D1 receptor antagonist SCH23390 on the behavior of PD rats, which may be exerted by changing the electrophysiological activity of EP. Key words: Parkinson’s disease; SCH23390; Movement disorders; Dopamine; Entopeduncular nucleus