Study Of Animal Model Of Schizophrenia By Electrically Stimulating VTA In Rats

Objective Excessive activity or supersensitivity of the central DA system is thought to be involved in the pathophysiology of schizophrenia . Ventral tegmental area (VTA) is source of two major dopaminergic systerm:mesolinbic systerm and mesocortical systerm .Ascending axonal projections from the DA neurons in the ventral tegmental area (VTA) are organized topographically, with the A10 cell group contributing to mesocorticolimbic projections and projecting to forebrain nuclei, including the nucleus accumbens (NAc),amygdala and prefrontal cortex (PFC). The study of characteristic activity of VTA may be the key to reveal the psychic activity in brain .in this article,we applied electric stimulation in VTA of rats to abtain animal models of schizophrenia,and investigated the role of typical antipsychotic drugs on the models ,explored further the relationship between VTA and etiology of schizophrenia.Methods 1)Thirty Wistar rats (,weighing 190 g±10 g) were stereotaxically implanted with bipolar electrode into basolateral nucleus of the right ventral tegmental area. The rats were allowed at least 14 days for a recovery period before the first stimulation. High-frequency Electrical stimulations (2-s trains of 1-ms pulses at 100Hz)were carried out when the rats were calm and at rest in the observation cage (in a state of light sleep state). These stimulations were delivered at an intensity of 10-100 mA in 10-mA steps at intervals of more than 3 min in order to exclude the effects of previous stimulations. Observing the changes of behavior of the rats and recording the EEG ,taking out twenty-four rats with psychotic behaviors and quantify the behavioral responses. (2) Rats were treated with different doses of haloperidol,SCH23390, clozapine and amphetamine, Changes in VTA stimulation-induced responses were compared with control responses. (3)Twenty rats were dibided into two groupsrpositive control group and treatment group(10 rats in each groups).Positive control group were removed bilateral VTA and PFC after 100μA stimulation; Treatment group were treated with HAL and 30 min later,were removed bilateral NAc and PFC after 100μA stimulation;Ten rats without any treatment as negative control group were removed bilateral NAc and PFC. The contents of DA,DOPAC and HVA were estimated in these two nuclei with HPLC.Results Abnormal behavior were induced by high-frequency stimulation in VTA,and were similar to that induced by psychostimulants such as amphetamine and cocaine ;the ECG are normal.,attenuated by DA receptor antagonists;Abnormal...