CONCEPTS & THEORY
Is doping of cognitive performance an anti-herbivore adaptation?
Alkaloids inhibiting acetylcholinesterase as a case
Institute of Environmental Sciences, Jagiellonian University, ul. Gronostajowa 7, Krak
ow, 30-387 Poland
Department of Arctic Biology, The University Centre in Svalbard, Longyearbyen, N-9171 Norway
Department of Wildland Resources, Utah State University, Logan, Utah 84322 USA
Citation: Ejsmond, M. J., and F. D. Provenza. 2018. Is doping of cognitive performance an anti-herbivore adaptation?
Alkaloids inhibiting acetylcholinesterase as a case. Ecosphere 9(2):e02129. 10.1002/ecs2.2129
Historically, people who study interactions between plants and herbivores focused on the eco-
logical costs and beneﬁts of synthesizing secondary metabolites. These compounds have diverse functions
including defenses against herbivores. Some plants produce alkaloids that act as acetylcholinesterase inhi-
bitors, increasing both the level and duration of action of the neurotransmitter acetylcholine with potential
toxic effects in insects and mammals. Yet, among a number of neuroactive plant chemicals, alkaloids that
inhibit acetylcholinesterase (AIA) display nootropic activities, that is, positively affect cognition, learning,
and memory in mammals. This creates a paradox: Neuroactive AIA, expected to punish herbivores,
enhance cognition, learning, and memory. A prevailing view is AIA are pesticides that adversely affecting
the nervous systems of herbivorous insects, and the positive inﬂuences in mammals are merely a by-
product of other functions. We review literature on the behavioral ecology of diet choice, food-aversion
learning, and neurophysiological actions of AIA in mammals to provide a more comprehensive view of
the adaptive signiﬁcance of AIA. These compounds act as anti-herbivory defenses that inﬂuence ﬂavor
(taste plus odor) preference/aversion, the formation of memories, and the feeding behavior of mammalian
herbivores. Thus, what appears from an insect standpoint to be an enigma makes sense for mammals: AIA
enable mammalian herbivores to quickly learn and remember speciﬁc plant(s) and the locations where
they ate those plant(s). We provide examples of AIA, synthesized by over 200 plant species in 16 families,
which affect learning and memory in mammals. Using 36 examples of acetylcholinesterase inhibitors
synthesized by plants in 58 families, we also show that acetylcholinesterase blockers contribute to anti-
herbivore chemical defense by affecting food-aversion learning and memory in mammalian herbivores.
We provide an evolutionary rationale for why natural selection may favor synthesis of chemicals that
positively affect mental functions of herbivores. Our hypothesis, which challenges the current view that
plant chemical defenses are aimed solely at destabilizing herbivore physiology, facilitates a broader
understanding of diet preferences and feeding behavior in mammalian herbivores.
Key words: acetylcholinesterase inhibitors; alkaloids; anti-herbivory chemical defense; aversion; cognition and
memory; diet choice; feeding behavior; learning; nootropics; plant secondary metabolites; plant-herbivore interactions;
Received 21 January 2018; accepted 24 January 2018. Corresponding Editor: Debra P. C. Peters.
Copyright: © 2018 Ejsmond and Provenza. This is an open access article under the terms of the Creative Commons
Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is