Nagarchi Khaleel1, Roopa Ravindranath1, BK Chandrasekhar Sagar2, Chittaranjan Andrade3
1 Department of Anatomy, St. John's Medical College, Bangalore, Karnataka, India
2 Department of Neuropathology, Electron Microscopy Laboratory, Bangalore, Karnataka, India
3 Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India
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|Date of Web Publication||7-May-2013|
| Abstract|| |
Background: In animal models, stress and depression are associated with excitatory changes in the amygdala; this aberrant neuroplasticity may represent increased fear learning, explaining the anxiety, fear, and related symptoms that characterize clinical depression.
Materials and Methods: In a pilot investigation, we treated adult, male, Wistar rats with sham electroconvulsive shocks (ECS; n=3), low-dose ECS (10 mC; n=3), and high-dose ECS (60 mC; n=3). The rats were sacrificed 1 month after the last of 6 once-daily ECS and, after dissection, sections of the basolateral amygdala were examined using transmission electron microscopy under low (×11,000) and high (×30,000) magnification.
Results: In each group, 4 fields were examined under low magnification and 6 fields under high magnification. The number of excitatory synapses and the ratio of excitatory to inhibitory synapses were both numerically lower with ECS than with sham ECS, and the effect was stronger in the high-dose ECS group (statistical analyses were not performed because this was a pilot study).
Conclusions: By reducing the number of excitatory synapses and the ratio of excitatory to inhibitory synapses, ECT (especially high-dose ECT) may reduce stress-induced excitatory changes in the amygdala. These changes may help explain a part of the benefits observed with ECT in conditions such as depression and post-traumatic stress disorder.
Keywords: Amygdala, depression, electroconvulsive therapy, electron microscopy, excitatory synapses, inhibitory synapses, neuroplasticity, posttraumatic stress disorder
|How to cite this article:|
Khaleel N, Ravindranath R, Chandrasekhar Sagar B K, Andrade C. Images in electroconvulsive therapy: Pilot impressions suggesting that ECT reduces excitatory synapses in the basolateral amygdala. Indian J Psychiatry 2013;55:204-5
|How to cite this URL:|
Khaleel N, Ravindranath R, Chandrasekhar Sagar B K, Andrade C. Images in electroconvulsive therapy: Pilot impressions suggesting that ECT reduces excitatory synapses in the basolateral amygdala. Indian J Psychiatry [serial online] 2013 [cited 2020 Feb 25];55:204-5. Available from: http://www.indianjpsychiatry.org/text.asp?2013/55/2/204/111471
| Introduction|| |
Histological studies in stressed animals and in animal models of depression demonstrate aberrant neuroplastic changes in the basolateral amygdala: there is an increase in dendritic arborization and synaptogenesis.  These changes perhaps represent fear learning and hence the anxiety, fear, and avoidance behavior displayed by patients with depression or post-traumatic stress disorder (PTSD).  Electroconvulsive therapy (ECT) is effective in both these disorders. , Does ECT reduce amygdalar excitability? We conducted a small, pilot, electron microscopy study to examine the amygdalar effects of ECT.
| Materials and Methods|| |
Adult, male, Wistar rats (180-250 g) were treated with 6 once-daily electroconvulsive shocks (ECS) in each of three conditions: sham ECS (n=3), low-dose ECS (10 mC; n=3), or high-dose ECS (60 mC; n=3). ECS was administered through saline-soaked, earclip electrodes using the Niviqure ECT device (Niviquire Meditech, Bangalore, India). The rats were housed under standard laboratory conditions and, 1 month after the last true or sham ECS, they were sacrificed and the amygdalae were dissected out. Sections of the basolateral amygdalae were later examined using transmission electron microscopy (TEM) under ×11,000 and ×30,000 magnification. There were 4 sections examined under ×11,000 and 6 under ×30,000 for each of the 3 treatment groups.
| Results|| |
A systematic count identified a total of 47 excitatory and 3 inhibitory synapses in the sham ECS group, yielding an excitatory to inhibitory synapse ratio of 15.7; these figures were 50 and 6 (ratio, 8.3) for low-dose ECT, and 35 and 4 (ratio, 8.8) for high-dose ECT.
A systematic count identified a total of 18 excitatory and 3 inhibitory synapses in the sham ECS group, yielding an excitatory to inhibitory synapse ratio of 6; these figures were 20 and 2 (ratio, 10.0) for low-dose ECT, and 14 and 4 (ratio, 3.5) for high-dose ECT.
We present representative low magnification TEM images obtained from sham [Figure 1]a, low-dose ECS [Figure 1]b, and high-dose ECS [Figure 1]c rats. The images show a decrease in the ratio of excitatory to inhibitory synapses in the ECS conditions relative to the sham condition.
|Figure 1: Transmission electron microscopy images, obtained at ×11,000 magnification, showing excitatory (squares/rectangles) and inhibitory (circles) synapses in rats treated with 6 once‑daily sham (a), low dose (10 mC) (b), or high dose (60 mC) (c) electroconvulsive shocks|
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| Discussion|| |
These pilot data suggest that there are two important changes in the basolateral amygdala that are detectable as long as 1 month after 6 once-daily ECS: (1) A decrease in the ratio of excitatory to inhibitory synapses and (2) a decrease in the absolute number of excitatory synapses. These changes are more evident with high-dose ECS than with low-dose ECS. These findings are congruent with our earlier report that there is attenuation of the density of apical dendritic arborization in rats 1 month after receiving 6 once-daily high dose ECS. 
The implication of our findings in these two studies is that at least a part of the mechanism of action of ECT in conditions such as depression and PTSD , may arise from a dampening effect of ECT on amygdalar neurotransmission, resulting from a decrease in the number of excitatory synapses in the basolateral amygdala, a decrease in the ratio of excitatory to inhibitory synapses, and a decrease in the density of apical dendritic arborization.
| Acknowledgments|| |
We acknowledge with thanks the assistance provided by the Mrs. Hemavathy and Mr. Ramesh, technical staff in the Electron Microscopy Laboratory, Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore.
| References|| |
|1.||Andrade C, Rao NS. How antidepressant drugs act: A primer on neuroplasticity as the eventual mediator of antidepressant efficacy. Indian J Psychiatry 2010;52:378-86. |
|2.||Sackeim HA, Prudic J, Devanand DP, Kiersky JE, Fitzsimons L, Moody BJ, et al. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. N Engl J Med 1993;328:839-46. |
|3.||Margoob MA, Ali Z, Andrade C. Efficacy of ECT in chronic, severe, antidepressant- and CBT-refractory PTSD: An open, prospective study. Brain Stimul 2010;3:28-35. |
|4.||Khaleel N, Roopa R, Smitha JS, Andrade C. Images in electroconvulsive therapy: ECT attenuates dendritic arborization in the basolateral amygdala. J ECT 2013. In press. |
Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None