The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 18 No. 5 • September 2015


AGGRESSION AND THE CHOLINERGIC NERVOUS SYSTEM

Aggression is part of human nature, not to be considered something harmful in itself. It all depends on what the aggression is used for. A mother protecting her infant is a type of well-known aggression and can serve a beneficial effect. Active self defense in the face of attack is another type of aggression that you had better have or you’re a sitting duck. In fact, I think it’s fair to say that if people didn’t have the ability to be aggressive in their own defense, the human species (or any species, for that matter) would have died out long ago. So aggression is a type of behavior that is necessary and is under the control of a number of neurotransmitters that both promote it and inhibit it, These includes serotonin, noradrenaline, and the cholinergic nervous system, among many others. Yes, it is very complicated and it is a wonder that people are able to live in a generally peaceful way among large numbers of other people. Not as peacefully as bonobos, for example, but perhaps (I (Sandy) speculate) the cholinergic system can offer a clue in that respect since it regulates both aggression and sexual activity and might act as a switch between these to the benefit of bonobos that would rather f__k than fight.

Early recognition of the cholinergic nervous system’s connection to the regulation of aggression was discussed in the classic book we have been talking about here. This is a 36 year old book and just shows you what three genius editors could do in giving an overview of a field that it seems these many years later has hardly penetrated the consciousness of many scientists, let alone laypeople.

The author of this section of the book (same author of the material on sexual activity we have discussed here) has this to say about aggression and the cholinergic nervous system: “Whether applied to several brain structures, particularly limbic brain structures or administered systemically, cholinergic (mostly muscarinic) agonists and/or anti-ChEs [anticholinesterases] cause aggression or facilitate experimentally induced aggression, whether of affective [emotional aggression that can be induced in small rodents by footshock or isolation] or predatory type [like the mouse killing behavior of rats]. Of interest in this context is the recent investigation of aggression induced in monkeys by small intravenous doses (6.25-25 μg/kg) of physostigmine [a cholinesterase inhibitor].” Long story short, a dominant monkey and a subordinate monkey were paired together, and one of the pair received physostigmine, which enhanced the aggressive action of the animal receiving it, whether that was the subordinate or the dominant animal, though it is reported that the effect was greater in the dominant animal. When the subordinate monkey got the drug, it reversed the hierarchical status of that animal. If this sounds familiar to you, like much more recent experiments that have produced similar results in monkeys treated with serotonergic drugs, it is likely due to the fact that activation of the cholinergic system increases the release of serotonin. But the old study with cholinergic drugs has been around for decades and seems to have been pretty well forgotten.

The author concludes this section of his part of the book by saying, “...it may be predicted that when ACh [acetylcholine] accumulation results as a consequence of a cholinergic diet, facilitation or induction of aggression should follow, as in this situation ACh would act as a cholinergic agonist.” A cholinergic diet might include a lot of eggs (with the choline largely contained in the yolks as phosphatidylcholine) or liver (yech).

Indeed, there is a very large scientific literature on the influence of cholinergic agonists on aggression, though there seems to be no general awareness of what this might mean in particular instances of human aggression. For example, a 2015 paper (Chen, 2015) reports that plasma butyrylcholinesterase regulates ghrelin to control aggression. Butyrylcholinesterase is an enzyme that also hydrolyzes acetylcholine (as does acetylcholinesterase) but at a higher concentration. Male BALB/c mice that had high levels of plasma butyrylcholinesterase (and thus decreased acetylcholine) as a result of gene transfer exhibited sharply reduced plasma ghrelin and surprised the paper’s authors by fighting less, both spontaneously and in a resident/intruder provocation model. On the other hand, mice with the BChE gene deleted had increased ghrelin and had a lot more fights. There was no mention of the early studies on the cholinergic system and aggression. It is almost as if the very early studies on aggression and the cholinergic system had been lost somewhere.

Reference

  • Chen, Gao, Geng, et al. Plasma butyrylcholinesterase regulates ghrelin to control aggression. PROC NATL ACAD SCI U S A. 112(7):2251-6 (2015).

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