Effects of propofol on expression of hippocampal neuronal nitric oxide synthase and carboxy-terminal PDZ ligand of neuronal nitric oxide synthase in stressed rats undergoing electroconvulsive shock

J ECT. 2013 Dec;29(4):297-302. doi: 10.1097/YCT.0b013e318290fa17.

Abstract

Objectives: This study aimed at investigating the effects of propofol on the expression of hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) in stressed rats after electroconvulsive shock (ECS).

Methods: Sprague-Dawley rats were stressed repeatedly for 28 days to establish a stressed model. Forty stressed rats were randomly divided into 4 groups (n = 10 for each group): the stressed group (unapplied group), propofol group (applied with intraperitoneal injection of propofol 80 mg/kg for 7 days), ECS group (applied with ECS and intraperitoneal injection of normal saline 8 mL/kg), or propofol + ECS group (applied with ECS and intraperitoneal injection of propofol 80 mg/kg). Sucrose preference test, open-field test, and Morris water maze were used to assess behavioral changes. Immunohistochemistry was carried out to measure the expression of nNOS and CAPON in hippocampal CA1, CA3, and DG areas.

Results: Rats in the ECS and propofol + ECS groups had higher sucrose preference percentages and open-field scores when compared with the stressed group. Rats in the ECS group exhibited longer escape latency, shorter space exploration time, up-regulated expression of nNOS, down-regulated expression of CAPON, and increased ratio of nNOS/CAPON in hippocampus. Compared with the ECS group, the propofol + ECS group exhibited shorter escape latency, longer space exploration time, down-regulated expression of nNOS, up-regulated expression of CAPON in hippocampus, and lower nNOS/CAPON values.

Conclusions: Propofol may alleviate ECS-induced impairment of learning and memory in stressed rats by inhibiting excessive expression of nNOS and enhancing the expression of CAPON to maintain the balance between nNOS and CAPON in hippocampus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Depressive Disorder / drug therapy
  • Depressive Disorder / metabolism
  • Depressive Disorder / therapy
  • Disease Models, Animal
  • Electroshock / methods*
  • Exploratory Behavior / drug effects
  • Food Preferences / drug effects
  • Hippocampus / drug effects*
  • Hippocampus / enzymology
  • Hypnotics and Sedatives / pharmacology
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / diagnosis
  • Memory Disorders / etiology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type I / metabolism*
  • Propofol / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / drug therapy
  • Stress, Psychological / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Hypnotics and Sedatives
  • NOS1AP protein, rat
  • Nitric Oxide
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Propofol