Effects of D2 receptor antagonist haloperidol on hippocampal neuronal apoptosis in a rat model of temporal epilepsy

BACKGROUND: Dopamine receptors are divided into D1 and D2 subgroups. It has been reported that D2 receptors resist neural toxicity induced by excitatory amino acids and muscarine, and also alleviate epilepsy attacks following pilocarpine treatment. However, it has not yet been established whether D2 receptors regulate temporal epilepsy.OBJECTIVE: To observe the effects of the D2 antagonist halopefidol on hippocampal neuronal apoptosis and electrical brain activity in a rat model of kainic acid-induced temporal epilepsy.DESIGN, TIME AND SETTING: Randomized grouping and histopathological study were performed at the Neurology Medicine Institute of Zhujiang Hospital, Southern Medical University from August to December 2004.MATERIALS: Twenty-five adult, male, Sprague Dawley rats were selected for the present study. Kainic acid (Sigma, USA) was injected into the right lateral ventricle to establish models of temporal epilepsy. A PowerLab multiplying channel electrophysiolograph was provided by AD Instruments, Australia.METHODS: The rats were randomly divided into 5 groups (n = 5): control, model, haloperidol hippocampus, haloperidol striatum, and haloperidol substantia nigra. Temporal epilepsy was established in all rats except the control group. Haloperidol was slowly injected into the hippocampus, striatum and substantia nigra, respectively, in three different injection groups. Normal saline was injected into the fight lateral ventricle of the control rats.MAIN OUTCOME MEASURES: Hippocampal apoptosis was observed on the day 3 of treatment using TUNEL staining. Changes in electroencephalogram at 0, 0.5, 2, 6, and 12 hours following treatment onset were observed using a PowerLab multiplying channel electrophysiolograph. Animal behaviors were classified according to the Racine criteria.RESULTS: Twenty-five rats were included in the final analysis. Seizures did not occur in the control group. In the model group, 10 minutes alter kainic acid injection to the lateral cerebral ventricle, epilepsy seizures occurred and reached a peak within one hour. Hippocampal neuronal apoptosis occurred following epilepsy, in particular on day 3. Following halopefidol injection, hippocampal neuronal apoptosis increased, in particular in the haloperidol hippocampus group, and was significantly greater than the model group (P < 0.05).CONCLUSION: Results suggested that D2 receptors inhibited temporal epilepsy. The hippocampal D2 receptors exhibited the strongest influence on temporal epilepsy in the hippocampus, followed by the substantia nigra and the striatum.