The Effects And Underlying Mechanisms Of Haloperidol On High-voltage Electroencephalogram Spindles In The Freely Moving Rats

Background and objective:Recently, various neuronal oscillations in brain which reflect the activitiesand mutual connection in neurons are attracting considerable attention. Thesynchronous activity of oscillating networks is now viewed as the critical"middle ground" linking single-neuron activity to behavior and plays animportant role in the information processing including motor activity, sensory,perception, memory and even consciousness. Synchronous oscillation in thecortex is increasing recognized as one of vital mechanisms of motor activityorganization. Many oscillatory activities are associated with special brain states,so the study of different oscillation activities helps to understand the brain workprinciple. The high-voltage spindle (HVSs), one of oscillations, is a good tool toachieve this goal.High-voltage spindle (HVSs) is7-12Hz oscillation, which exhibit a characteristic spike-and-wave pattern and appear in waking-immobile state. Itdisappears immediately after moving. HVSs can be recorded in many regionssuch as the cortex, thalamus, reticular formation, cerebellar hemisphere andbasal ganglia which indicate that it may have important function. However, thefunctional relevance of HVSs was still controversial. Previous research showsthat many neurotransmitters in the brain systems such as noradrenergic,5-HTand cholinergic brain systems are related to the regulation of the high-voltagespindles. However, the modulation of HVSs by dopaminergic system whichmediates several important physiological functions in the central nervous system(CNS) is less studied. If the dopamine receptors relate to the regulation of HVSs,it is still not clear whether dopamine D1-like receptor or D2-like receptorinvolved in? What is the possible function of HVSs? These problems areexpected to be studied.Methods:In this study, continuous video, neocortical electroencephalography (EEG)and facial electromyography (EMG) were recorded simultaneously in the freelymoving rats. In the first part, we studied the effects of haloperidol on catalepsy,incidence and duration of cortical HVSs, the corresponding facial activities andthe facial EMG activities. In the second part, we studied the effects of dopaminereceptors agonist or antagonist on the neocortical high-voltage spindles.Results:(1) Spontaneous cortical HVSs were recorded in behavioralwaking-immobility rats, its frequency was ranged from7to12Hz andits duration was ranged from0.5to16seconds. During corticalHVSs, facial wisher twitching (WT) appeared occasionally andrhythmic activities were recorded in corresponding facial EMG. The duration of rhythmic muscular activities was one-third to a half of thecortical HVSs.(2) Haloperidol caused catalepsy at the dosage of1.0mg/kg and3.0mg/kg,the latency was353.88±46.69s and578.75±49.00s, respectively. Thedifference among three groups were significantly (P=0.000). Thelatency of low dose group significantly shorter than the high dosegroup (P=0.000).(3) Haloperidol increased rang and intensity of whisker twitching. Therhythmic muscular activities in EMG were increased and its durationwas prolonged as long as the corresponding cortical HVSs.(4) Compared with control group, haloperidol (1.0-6.0mg/kg)significantly enhanced cortical HVSs (P<0.01). Haloperidol at3.0mg/kg was more effective in increasing cortical HVSs than that of1mg/kg and6mg/kg (P<0.01). There was no difference between1mg/kg and6mg/kg of haloperidol on enhancement effect on HVSs(P=0.081).(5) Compared with control group, apomorphine (0.1-0.5mg/kg)significantly decreased cortical HVSs (P<0.01). Apomorphine at0.5mg/kg was more effective in decreasing cortical HVSs than that of0.1mg/kg (P<0.01).(6) Compared with haloperidol only group, apomorphine (0.5mg/kg)significantly antagonized the enhancement effect on cortical HVSsproduced by haloperidol (1.0-6.0mg/kg)(P<0.01).(7) Compared with control group, there was no significantly effect ofSCH23390(0.5-10.0mg/kg) on cortical HVSs (P=0.19).Conclusion: (1) Haloperidol can cause rat catalepsy which can be used for mimickingakinesia and rigidity of Parkinson’s disease (PD). There is a positivecorrelation between the intensity and latency of catalepsy and thedosage of haloperidol.(2) Haloperidol can increase the number and duration of cortical HVSs aswell as enhanced the intensity of facial whisker twitching (WT) andprolonged the facial rhythmic muscular activities in EMG.(3) The abnormal cortical HVSs and corresponding facial rhythmicmuscular activities may be the electrophysiology indicator ofextrapyramidal symptoms (EPS) induced by antipsychotic drugs.(4) While dopamine D2-like receptor antagonist enhanced cortical HVSsand dopamine receptor agonist decreased cortical HVSs, dopamineD1-like receptor had no effect on cortical HVSs, indicating dopamineD2-like receptor not D1-like receptor contribute to cortical HVSsregulation.