Reduced Synaptic Plasticity Contributes to Resistance Against Constant-Stimulus Electroconvulsive Treatment in a Rat Model of Stress-Induced Depression

Abstract

Purpose: Depression is a common mood disorder in humans worldwide. Electroconvulsive therapy (ECT) remains the most effective treatment for patients with drug-resistant or severe depression; however, during ECT, electrical resistance can occur, antagonizing ECT efficacy. We aimed to investigate how depressed patients develop resistance to electric shocks during ECT.

Methods: Rats exposed to chronic unpredictable stress exert similar impairments in hippocampal synaptic plasticity as those in depressed humans, including hippocampal neuronal atrophy and reduced synaptic function and synapse-related proteins. Therefore, a rat model was used to model depressive-like behaviors in the current study. Depression-like behavior was stimulated in Sprague Dawley (SD) rats that were then randomized into six groups: control group (C); a rat model of stress-induced depression group (D); and four groups in which a rat model of stress-induced depression received one, three, five, or seven electroconvulsive shocks (ECS; DE1, DE3, DE5, and DE7). The sucrose preference test (SPT) and Morris water maze (MWM) were utilized to evaluate anhedonia and spatial learning and memory in rats, respectively. Synaptic plasticity was recorded electrophysiologically in terms of field excitatory postsynaptic potential (fEPSP) and long-term potentiation (LTP).

Results: The rat model of stress-induced depression triggered a decrease in the sucrose preference percentage (SPP) and the baseline fEPSP slope relative to those observed for the C group, and these changes were significantly rescued by ECT in a shock number-dependent manner within five shocks. However, the rat model of stress-induced depression displayed an increase in the escape latency and a decrease in space exploration time, in addition to decreased LTP relative to those in the C group, which was further augmented by ECT in a shock number-dependent manner within five shocks.

Conclusion: Changes in synaptic plasticity might be responsible for the development of resistance against constant-stimulus ECT in a rat model of stress-induced depression.

Keywords: depression; electrical resistance; electroconvulsive shocks; synaptic plasticity.

Figure 1

Experimental timeline.

Figure 2

SPP before and after ECSs. *P < 0.05 vs C. ^#P < 0.05 vs D. ^∇P < 0.05 vs DE1. ^ΔP < 0.05 vs DE3.

Figure 3

MWM outcomes for different groups. (A) Swimming speed. (B) Escape latency. (C) Space exploration time. *P < 0.05 vs C. ^#P < 0.05 vs D. ^▽P < 0.05 vs DE1. ^ΔP < 0.05 vs DE3.

Figure 4

Baseline fEPSP in the hippocampal SC-CA1 pathway. (A) Diagrammatic representation of a hippocampal cross-section showing the stimulating and recording electrodes. (B) Field potentials recorded from hippocampal SC-CA1. The baseline fEPSP slope was measured for the region between the red lines. (C) Comparison of baseline fEPSP slopes. *P < 0.05 vs C. ^#P < 0.05 vs D. ^▽P < 0.05 vs DE1. ^ΔP < 0.05 vs DE3.

Figure 5

LTP in the hippocampal SC-CA1 pathway. (A) Post-fEPSP after high-frequency stimulation. The black trace indicates the pre-stimulation baseline; the red trace indicates the post-stimulation recording. Horizontal scale bar, 5 ms; vertical scale bar, 1 mV. Arrows indicate the stimulus (200 pulses at 100 Hz). (B) Comparison of post- fEPSP. *P < 0.05 vs C. ^#P < 0.05 vs D. ^▽P < 0.05 vs DE1. ^ΔP < 0.05 vs DE3.