Evaluating the Effect of Electroconvulsive Shock and Duloxetine Combination Therapy on Behavioral, Cardiovascular, and Brain Oxidative Stress Markers in the Rats

Background: Electroconvulsive Therapy (ECT) as a well-established and effective therapeutic approach for the treatment of various psychiatric disorders is an excellent option to treat the major depressive disorder (MDD). The goal of this experimental study was to determine the possible sides effects of electroconvulsive shock (ECS) and duloxetine, a serotonin-norepinephrine Reuptake Inhibitors (SNRIs), and evaluate the safety of this therapeutic approach on behavioral factors, cardiovascular function, and brain oxidative stress markers on mice. Materials and Methods: Animals were divided into different groups receiving either ECS or different doses (10, 20, 40, 80, or 120 mg) of duloxetine alone or together. We evaluated the behavioral factors associated with administration of ECS with or without duloxetine. In addition, we monitored the ECGs (electrocardiogram) of animals prior to and after the experiment and also evaluated the oxidative stress markers including TAC, MDA, and GSH mice’s brains. Results: We did not detect any significant differences in terms of heart rate, RR interval, PR interval, QT, or corrected QT (QTc) between groups that received different doses of duloxetine in combination with ECS compare to the control group. Our findings suggest that while administration of ECS solely increased the oxidative stress markers and decreased the antioxidant capacity of the brain, a combination of duloxetine and ECS at certain doses alleviates the oxidative stress condition and increases the antioxidant capacity of the brain. Conclusion: Overall, this study suggests that the combination of ECS and duloxetine is safe and considerable for further studies on human subjects.

Electroconvulsive Shock, but Not Transcranial Magnetic Stimulation, Transiently Elevates Cell Proliferation in the Adult Mouse Hippocampus

Hippocampal plasticity is hypothesized to play a role in the etiopathogenesis of depression and the antidepressant effect of medications. One form of plasticity that is unique to the hippocampus and is involved in depression-related behaviors in animal models is adult neurogenesis. While chronic electroconvulsive shock (ECS) strongly promotes neurogenesis, less is known about its acute effects and little is known about the neurogenic effects of other forms of stimulation therapy, such as repetitive transcranial magnetic stimulation (rTMS). Here, we investigated the time course of acute ECS and rTMS effects on markers of cell proliferation and neurogenesis in the adult hippocampus. Mice were subjected to a single session of ECS, 10 Hz rTMS (10–rTMS), or intermittent theta burst stimulation (iTBS). Mice in both TMS groups were injected with BrdU 2 days before stimulation to label immature cells. One, 3, or 7 days later, hippocampi were collected and immunostained for BrdU + cells, actively proliferating PCNA + cells, and immature DCX + neurons. Following ECS, mice displayed a transient increase in cell proliferation at 3 days post-stimulation. At 7 days post–stimulation there was an elevation in the number of proliferating neuronal precursor cells (PCNA + DCX +), specifically in the ventral hippocampus. iTBS and rTMS did not alter the number of BrdU + cells, proliferating cells, or immature neurons at any of the post-stimulation time points. Our results suggest that neurostimulation treatments exert different effects on hippocampal neurogenesis, where ECS may have greater neurogenic potential than iTBS and 10–rTMS.

Electroconvulsive Shock Does Not Impair the Reconsolidation of Cued and Contextual Pavlovian Threat Memory

Existing memories, when retrieved under certain circumstances, can undergo modification through the protein synthesis-dependent process of reconsolidation. Disruption of this process can lead to the weakening of a memory trace, an approach which is being examined as a potential treatment for disorders characterized by pathological memories, such as Post-Traumatic Stress Disorder. The success of this approach relies upon the ability to robustly attenuate reconsolidation; however, the available literature brings into question the reliability of the various drugs used to achieve such a blockade. The identification of a drug or intervention that can reliably disrupt reconsolidation without requiring intracranial access for administration would be extremely useful. Electroconvulsive shock (ECS) delivered after memory retrieval has been demonstrated in some studies to disrupt memory reconsolidation; however, there exists a paucity of literature characterizing its effects on Pavlovian fear memory. Considering this, we chose to examine ECS as an inexpensive and facile means to impair reconsolidation in rats. Here we show that electroconvulsive seizure induction, when administered after memory retrieval, (immediately, after 30 min, or after 1 h), does not impair the reconsolidation of cued or contextual Pavlovian fear memories. On the contrary, ECS administration immediately after extinction training may modestly impair the consolidation of fear extinction memory.