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Many antidepressants alter neurotransmission of monoamines, which might — or might not — be a mechanism of action in improving depression. Evidence is accumulating that other neurophysiologic processes might be more relevant, including second messenger signaling, neurotrophic factors, neuroendocrine factors, and epigenetic mechanisms (Nature 2008; 455:890). In an elegant series of animal experiments, researchers explored the role of the pH-responsive sodium channel, acid-sensing ion channel-1a (ASIC1a), in an established model of depression and antidepressant response.
The researchers used several behavioral tests as depression analogues. Compared with ASIC1a-homozygous mice, ASIC1a-knockout mice had less immobility in the tail-suspension an…