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Cholinergic overdrive has long been theorized to play a role in the pathophysiology of depression (e.g., Psychosom Med 1974; 36:248), and anticholinergic drugs, such as the nonselective muscarinic antagonist scopolamine, have been postulated to have antidepressant properties. These researchers further examined the effect of scopolamine in a series of rat studies.
Both scopolamine and telenzepine, a selective antagonist of the M1 receptor, reversed depression-like behaviors in an established animal model. Similar to ketamine, scopolamine increased signaling by the mammalian target of rapamycin complex-1 (mTORC1), a crucial transcription agent (see NEJM JW Psychiatry Sep 9 2013), and increased the frequency of excitatory postsynaptic currents,…