Amino Acids Neurotransmitter Mechanism Of Propofol On Reducing Learning Memory Impairment Of Depressed Rats Undergoing Electroconvulsive Therapy

Objectives To observe the effect of propofol on learning abilities and memory of depressed rats after ECT,detecting the expression of BDNF mRNA, GAD65 and the contents of Glu and GABA. To investigate amino acids neurotransmitter mechanism of propofol on reducing learning abi- lities and memory impairment of depressed rats undergoing ECT.Methods Sixty adult male SD rats weighing 200-250g were randomly divided into five groups(n=12): control group (group C), depressed group (group D), propofol group (group P), ECT group (group E) and propofol combined with ECT group (group M). The depression model of rats was produced by separation and chronic unpredictable mild stress. After the model was succeeded, the animals of group C and D were administered 0.9% NS(10ml/kg, i.p.);the animals of group P were administered with propofol (100mg/kg, i.p.); the animals of group E were administered ECT once on alternate days for 6 times;the animals of group M received ECT with propofol (100mg/kg, i.p.) on alternate days for 6 times. Then we studied anxiety-related behaviour and exploration of rats in the open field, and evaluated spatial learning memory in Morris Water Maze. 6 samples in each group were randomly selected for determination of the glutamate, GABA and expression of GAD65 in hippocampus by high performance liquid chromatography (HPLC) and immunohistochemis- try, respectively. The expression of BDNF mRNA was determinated by Real-time PCR.Results (1) Open-field test: Pre-model, there were no significance of ambulation and rearing in open field test between each groups (P>0.05). Post-model, there were no significance of ambulation and rearing in open-field test between each group except group C (P >0.05), and it was decreased when compared with group C (P<0.05). Post-treatment, ambulat- ion and rearing of Open-field test were significantly increased in group E and group M compared with group D (P<0.05). (2) Morris Water Maze test: Post-model, there were no significance of the evasive latency (EL) and swimming time percentage in platform quadrant (STP) of Morris Water Maze in each group except group C (P>0.05). Post-treatment, the EL in group E was longer than that in group D and group M (P<0.05). The STP of rats in group E was smaller than that in group D and M (P<0.05). There were no significance in the EL and STP in groups D and M (P>0.05). (3) The expression of BDNF mRNA in hippocampus: The expression of BDNF mRNA was significantly decreased in group D compared with the ones in group C (P<0.05). The expression of BDNF mRNA was significantly incr- eased in group E and M compared with the ones in group D (P<0.05). (4) Glutamate, GABA contents and Glu/GABA ratios in hippocampus: Compared with group C, Glutamate contents in group D was increased, GABA contents in group D was decreased, Glu/GABA ratio was increased, Glutamate contents in group E was increased, GABA contents in group E was decreased, Glu/GABA ratio was decreased (P<0.05), There was no significant difference between group C and M (P>0.05). Compared with group D,glutamate contents in group E was decreased, GABA con- tents was increased,Glu/ GABA ratio was decreased (P<0.05), GABA contents in group M were increased,Glu/GABA ratios were decreased (P<0.05). When compared with group E, glutamate contents was increased, GABA contents was decreased, Glu/GABA was increased in group M (P<0.05). (5) The expression of GAD65 in hippocampus CA1 and CA3 areas by immuno -histochemistry: The expression of GAD65 in group D and group P was lower when compared with the one in group C (P<0.05), and there was no significance between group D and P (P>0.05). The expression in group E and was higher than that in group C (P<0.05), and the expression of GAD65 in group M was lower than that in group E (P<0.05).Conclusions (1) ECT and propofol combined with ECT may up-regulate the expression of BDNF mRNA in hippocampus to improve depression symptoms of depressed rats. BDNF pathway wouldn't partici- pate the mechanism of ECT impair learning memory. (2) Depression and ECT would disturb the balance between excitation and inhibition neurotr- ansmitter, thus learning abilities and memory was impaired. (3) Propofol inhibited the expression of GAD65 in hippocampus after ECT, and improved the balance between excitation and inhibition system to reduce the learning memory impairment of depressed rats after ECT.