Experimental Study Of Phencyclidine Induction Of Machin Exists Long-term Lack Of Sensory Gating And Dopamine Dysfunction

ObjectivePhencyclidine (PCP) is the antagonist of the noncompetitive Receptor of N-methyl-D-aspartate (NMDA), its main pharmacological action is to antagonizing the NMDA receptor, leads to the decrease of the functional activity of Glu neurons projecting on the cerebral cortex and under the cortex.,appear a series of negative symptoms of schizophrenia and cognitive dysfunction such as apathy, withdrawal from social activities, willpower and so on, reflective causes the midbrain dopamine (DA) of the limbic system hyperfunction at the same time, resulting positive symptoms in delusions, hallucinations, delusions,impulse[1,2]. More and more studies show that Glu-DA neurotransmitter disorder is closely related to the pathological and physiological mechanism of schizophrenia, cognitive dysfunction is one of the three core symptoms of schizophrenia, sensory gating (Sensory gating, SG) is the core mechanism of cognitive dysfunction. The purpose of this experiment is intended to study machin exposed to PCP whether exist sensory gating defects a long time, and dopamine (DA) system function disorder.MethodWe test pregnant female machin exposured to PCP 2 years ago (given PCP 0.3 mg/kg intramuscular injection, twice a day, for two weeks). The experiment is divided into three parts, Randomly selected 6 machin for the experimental group-chronic PCP group, and 6 machines with same age as normal control group, and four blank saline control group, Under continuous propofol intravenous anesthesia, give the experiment group and the control one different dose dopamine agonists-bromocriptine, dopamine receptor antagonist-haloperidol and pcp,and scalp with eight records electrodes, which located in bilateral forehead department (F3, F4), temporal (FT7, FT8), the top (CP3, CP4), occipital (O1,02), reference electrode (A) the earlobe, forehead grounding (D), quiet, slightly dark environment give conditions-stimulate (S1-S2) double-sound stimulation and use computer to record, and to pick up the event related potential (Auditory EvokedPotential, AEP), the interval in the double-sound stimulation is 500ms, and the interval of two double-sound stimulation is 5-10s, sound intensity of 75 dB (background noise:45dB).. After the experiment, off-line analysis of 8 parts bilateral frontal lobe, temporal lobe, parietal lobe, occipital lobe, statistical analysis for SG.Results1. The experiment one (Bromocriptine, Brom):Low dose group (0.313 mg/kg), chronic PCP group and normal control group and saline blank group of SG values in eight regions without obvious difference; Middle dose group (0.625 mg/kg) chronic PCP group of left temporal lobe (FT7) sensory gating value is significantly higher than the normal control group, chronic PCP group, the right temporal lobe of and normal control group (FT8) sensory gating value more saline control group obviously higher; High dose group (1.25 mg/L/kg), the left frontal lobe (F3) of chronic PCP group of sensory gating value is relatively high in health and normal control group obviously;2. Experiment 2 (haloperidol, Hal):Low dose group (0.001 mg/L/kg), the right frontal lobe (F4) of chronic PCP group SG values significantly lower than the normal control group; Middle dose group, chronic PCP group and normal control group has no difference between the various brain regions SG values, Chronic PCP group F4 (right amount) SG values is saline control group obviously higher, normal control group F4 area SG and brine were significantly difference; High dose (0.05 mg/kg) of chronic PCP group right temporal lobe (FT8) SG values higher than the normal control group;3. Experiment 3 (Phencyclidine, PCP):0.3 mg/kg, compared with normal control group, no difference between the chronic PCP SG group, chronic PCP group in FT8 SG values (right temporal) area significantly greater than saline group and normal control group CP3 (top left) SG significantly higher value than saline group.ConclusionThe experimental results shown that:machin repeated exposure in PCP, two years later, the sensory gating is still flawed, The effect of PCP damage to machin’s SG ability may be with long-term effect, and the dopamine system play an important role in the pathophysiological changes, particularly in the frontal lobe, temporal lobe. Dopamine agonists significantly reduced its door control ability; the appropriate amount of dopamine receptor antagonist can improve door control ability, excess anount also damage sensory gating. It shows that PCP might lead to dopamine under-utilization frontal lobe and temporal lobe, subcortical overactive dopamine, the damage of sensory gating may be irreversible.