Abstract
Post-ictal emergence of slow wave EEG (electroencephalogram) activity and burst-suppression has been associated with the therapeutic effects of the electroconvulsive therapy (ECT), indicating that mere “cerebral silence” may elicit antidepressant actions. Indeed, brief exposures to burst-suppressing anesthesia has been reported to elicit antidepressant effects in a subset of patients, and produce behavioral and molecular alterations, such as increased expression of brain-derived neurotrophic factor (BDNF), connected with antidepressant responses in rodents. Here, we have further tested the cerebral silence hypothesis by determining whether repeated exposures to isoflurane anesthesia reduce depressive-like symptoms or influence BDNF expression in male Wistar outbred rats (Crl:WI(Han)) subjected to chronic mild stress (CMS), a model which is responsive to repeated electroconvulsive shocks (ECS, a model of ECT). Stress-susceptible, stress-resilient, and unstressed rats were exposed to 5 doses of isoflurane over a 15-day time period, with administrations occurring every third day. Isoflurane dosing is known to reliably produce rapid EEG burst-suppression (4% induction, 2% maintenance; 15 min). Antidepressant and anxiolytic effects of isoflurane were assessed after the first, third, and fifth drug exposure by measuring sucrose consumption, as well as performance on the open field and the elevated plus maze tasks. Tissue samples from the medial prefrontal cortex and hippocampus were collected, and levels of BDNF (brain-derived neurotrophic factor) protein were assessed. We find that isoflurane anesthesia had no impact on the behavior of stress-resilient or anhedonic rats in selected tests; findings which were consistent—perhaps inherently related—with unchanged levels of BDNF.
Highlights
Major depression is a highly disabling medical condition that largely contributes to the global disease burden [1]
Post-ictal EEG suppression has been proposed to predict the antidepressant effects of Electroconvulsive therapy (ECT) [26,27,28,29,30]
Already a single brief isoflurane anesthesia has demonstrated antidepressant-like effects in the forced swim test and learned helplessness model in rodents [44,45]
Summary
Major depression is a highly disabling medical condition that largely contributes to the global disease burden [1]. It is the most significant risk factor for suicides. One third of patients with major depression do not respond to prescription antidepressants, but for those who do, the therapeutic effects are evident with a delay of weeks or months of medication. Electroconvulsive therapy (ECT) remains among the most potent treatments for pharmacoresistant depression. Reported response rates to ECT are high, especially for melancholic depression [2,3,4]. ECT may produce adverse effects, such as retrograde amnesia, headache, and nausea [2]
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