Abnormal Gamma Oscillation Of Machins Induced By Chronic Administration Of Phencyclidine And Dopaminergic Effect On Gamma Oscillation

Objectives:Schizophrenia is considered a neurodevelopmental and neurodegenerative disorder. Schizophrenia is identified clinically by the appearance of positive symptoms (psychosis, hallucinations, paranoia) and negative symptoms (flat affect,impaired attention and motivation). However, deficits in fundamental cognitive processes (working memory, executive function) are currently believed to serve as the core feature of this disease. It is assumed that an imbalance of excitatory and inhibitory (E-I) activity induced by dysfunction of glutamatergic (Glu) and dopaminergic (DA) transmission resulted in both positive symptoms and inhibitory symptoms. These two kinds of neurons can interaction through γ-aminobutyric acid(GABA) interneurons. Numerous subtypes of GABAergic interneurons which have been characterized throughout the brain, based upon their anatomical, physiological,and molecular features. However, abnormal firing of Parvalbumin (PV)-positive GABAergic interneurons has been associated with aberrant gamma oscillation leading to impaired cognitive function. Studies in healthy individuals have provided evidence that gamma-band responses play an important role in neuropsychological functions,such as selective attention, multi sensory processing perceptual feature binding,Storage and retrieval of memory and working memory. And these damage happens to be the core symptoms of schizophrenia. Prefrontal aberrant gamma oscillations tend to be present for these patients. Abnormal gamma oscillations is not specific for schizophrenia, but it has important value on the diagnosis, treatment and predictor of functional outcomes. Previous research suggested N-methyl-D-aspartate (NMDA)receptors antagonist and dopaminergic agent impact gamma oscillations. However,inconsistent and findings exist. PCP is a nonspecific NMDA receptor antagonist can mimic the symptoms of schizophrenia preferably. The purpose of this experiment is to further verify the DA and Glu neurotransmitters exert influence over prefrontal gamma oscillations of chronic PCP machins.Methods:We record EEG signal by scalp electrodes implanted recording device. Two electrodes respectively placed in the forehead (F3, F4). Ground electrode set between arcus superciliaris (D), reference inserted lobulus auriculae (A). The paired-sound stimulation of Conditioning - testing paradigm was playing when recording (paired sounds interval is 500 ms, each pair of double sound stimulation for 5-10 s , the intensity of the sound of 75 dB, background noise: 45 dB). Randomly pick 4 participants of normal adult female machins, and 6 female machins applicated of repeated phencyclidine (PCP) as experimental group. First, compare control group with chronic PCP group baseline gamma power if there is a difference. And we applied three different doses of dopamine agonists bromocriptine (0.313 mg/kg, 0.625 mg/kg, 1.25 mg/kg) and dopamine receptor antagonists haloperidol (0.001 mg/kg,0.01 mg/kg, 0.05 mg/kg), records and extraction, calculation of objects prefrontal gamma band power, and statistical analysis.Results:1. The first experiment (control group vs. chronic PCP group baseline): Chronic PCP group baseline gamma oscillation power is significant lower than normal control group (Left: P=0.031,Right: P=0.030).2. The second experiment (Bromocriptine, Brom): Low dose (0.313 mg/kg) drug make left side prefrontal cortex gamma power increase firstly (P=0.024) then decline(P=0.046). In right side, after injection gamma band power in 30-60min is significant decrease than that in 0-30min(P=0.030).3. The third experiment (haloperidol, Hal) : High dose group, after injection both gamma power in 0-30min and 30-60min are significant increase in left side prefrontal(0-30min P=0.005、30-60min P=0.012). Gamma oscillation power in right prefrontal is significant increase during 0-30min than baseline(P=0.016)..Conclusions:Prefrontal lobe baseline gamma oscillation power of Chronic PCP machins is significant declined compared with normal control group. High dose of haloperidol can induce increasing prefrontal gamma oscillation associated with improved cognitive function. Low dosage of bro first increase objects’ prefrontal gamma oscillation then decrease. It may be contribute to differences between time and region.Repeated exposure to PCP caused a reduction dopamine utilization in the prefrontal cortex, a brain region that has long been associated with cognitive function.Disordered interaction of DA, Glu and GABA underline the pathophysiology of schizophrenia.