Aberrant regulation of dopamine system function in pre-adolescent schizophrenia rats

Objective To discuss the relationship of aberrant regulation of dopamine system function and schizophrenia. Methods Pregnant female Sprague Dawley rats were obtained at MAM(methylazoxymethanol acetate,diluted in saline,25mg/kg,i.p.)or saline was administered on GD17.Post-weaning,pre-adolescent rats were defined as postnatal day 35~40,whereas adult rats were over 10 weeks of age.Test 1:normal pre-adolescent rats and MAM-treated pre-adolescent rats;Adult normal rats and adult MAM-treated rats were implanted electrodes into ventral hippocampus(vHipp)to exam the effect of electric stimuli and apomorphine on locomotor activity of rats.Test 2:The spontaneous firing activity of dopamine neurons in VTA was recorded with normal or MAM-treated pre-adolescent rats,and the effect of MK-801 was observed on the dopamine neurons' firing activity. Results MAM-treated rats displayed a significant increase in the number of spontaneously active dopamine neurons throughout the VTA without significant changes in firing rate or burst firing,which could be withdraw by MK-801 injecting intra-vHipp.Adult MAM-treated rats presented an increase locomotor activity,and electric stimulation in vHipp results in an augmented locomotor were responsed to amphetamine administration followed.However,these behavioral changes did not happen on the pre-adolescent normal or MAM-treated rats. Conclusions The pathophysiological changes of schizophrenia have already happened in pre-adolescent period,which do not results the abnormal behavior activity till adult.Puberty is onset of dopamine receptors' functional changes.Therefore,pre-adolescent is a critical period for Prevention and screening of schizophrenia.