Propofol protects against impairment of learning-memory and imbalance of hippocampal Glu/GABA induced by electroconvulsive shock in depressed rats.

PURPOSE: General anesthetics are believed to induce amnesia. However, propofol can ameliorate cognitive deficits induced by electroconvulsive therapy (ECT), a treatment for mental disorders. This study aimed at investigating the possible molecular mechanism as well as the effects of propofol on learning-memory impairment in depressed rats induced by ECS (electroconvulsive shock, the analog of ECT to animals).
METHODS: Rats were treated with ECS (or sham ECS) pretreated with intraperitoneal injection of propofol (100 mg/kg) (or normal saline, 0.01 l/kg) after being treated with chronic unpredictable mild stresses to reproduce an animal model of depression. Sucrose preference test, open field test, and Morris water maze were used to assess behavioral changes. Hippocampal glutamate (Glu) and γ-aminobutyric acid (GABA) levels were measured with liquid chromatography, and glutamic acid decarboxylase 65 (GAD65) was assayed immunohistochemically. Additionally, rats undergoing ECS that were pretreated with pentobarbital sodium (45 mg/kg) were included for behavioral tests and electroencephalogram recording for comparison with rats undergoing ECS that were pretreated with propofol or normal saline.
RESULTS: ECS rats pretreated with propofol or pentobarbital sodium exhibited similar decreased seizure durations as compared with ECS rats pretreated with normal saline. ECS pretreated with normal saline aggravated learning-memory deficits whereas ECS pretreated with propofol or pentobarbital sodium did not. Rats undergoing ECS pretreated with propofol showed better memory than those undergoing ECS after pretreatment with pentobarbital sodium. ECS pretreated with normal saline downregulated the ratio of Glu/GABA and upregulated GAD65 expression; all these molecular changes were nearly normalized to the level of control group by ECS pretreated with propofol. There were no significant differences of depressive behaviors between groups treated with ECS.
CONCLUSIONS: The data suggest that propofol alleviated ECS-induced learning-memory impairment without interfering with the antidepressant efficacy of ECS, possibly by inhibiting excessive expression of GAD65 and maintaining the balance between glutamatergic and GABAergic amino acids neurotransmitters in the hippocampus.