ABSTRACT
For more than a century, acetylcholine has been postulated to be a factor in the regulation and etiology of affect. In 1889, Willoughby (1) reported a case in which pilocarpine, now known to be a muscarinic cholinergic agonist, was used to alleviate acute mania. Subsequently, in the late 1940s, 1950s, and early 1960s, a number of authors observed the anergic, inhibitory, anxiety-enhancing and mood-depressing effects of centrally acting cholinesterase inhibitors, compounds that inhibit the breakdown of acetylcholine. The mood altering effects of these compounds, used as insecticides in the agriculture industry and as nerve agents by the military, were described naturalistically and as tested in experimental settings. The observations by Grob et al. (2), Gershon et al. (3,4), Bowers et al. (5), and Rowntree et al. (6) led to a series of reports suggesting that increases in central acetylcholine led to depression, anxiety, and anergia.
