Revealing the paradox of drug reward in human evolution

Roger J Sullivan,Peter Hammerstein,Edward H Hagen

doi:10.1098/rspb.2007.1673

Abstract

Neurobiological models of drug abuse propose that drug use is initiated and maintained by rewarding feedback mechanisms. However, the most commonly used drugs are plant neurotoxins that evolved to punish, not reward, consumption by animal herbivores. Reward models therefore implicitly assume an evolutionary mismatch between recent drug-profligate environments and a relatively drug-free past in which a reward centre, incidentally vulnerable to neurotoxins, could evolve. By contrast, emerging insights from plant evolutionary ecology and the genetics of hepatic enzymes, particularly cytochrome P450, indicate that animal and hominid taxa have been exposed to plant toxins throughout their evolution. Specifically, evidence of conserved function, stabilizing selection, and population-specific selection of human cytochrome P450 genes indicate recent evolutionary exposure to plant toxins, including those that affect animal nervous systems. Thus, the human propensity to seek out and consume plant neurotoxins is a paradox with far-reaching implications for current drug-reward theory. We sketch some potential resolutions of the paradox, including the possibility that humans may have evolved to counter-exploit plant neurotoxins. Resolving the paradox of drug reward will require a synthesis of ecological and neurobiological perspectives of drug seeking and use.

Highlights

The use of psychoactive substances is one of the most perplexing human behaviours
Stimulants such as amphetamines and cocaine directly increase dopaminergic transmission in the nucleus accumbens (NAc); opiates inhibit GABAergic interneurons in the ventral tegmental area (VTA) by disinhibiting VTA dopamine neurons projecting to the NAc; and nicotine seems to activate VTA dopamine neurons both directly and indirectly via stimulation
We interpret the conserved function in human cytochrome P450 (CYP) enzymes, the statistical evidence of stabilizing selection and the existence of both species- and population-specific polymorphisms as evidence that humans have undergone relatively recent selection by plant toxins frequently encountered in local environments

Summary

INTRODUCTION

The use of psychoactive substances is one of the most perplexing human behaviours. Some substances cause immeasurable harm to individuals and societies (e.g. heroin) or impose a tremendous social burden in the form of preventable chronic illnesses (e.g. tobacco), while others appear to be mostly harmless and are widely enjoyed by people around the world (e.g. coffee and chocolate). Behaviours beneficial to an animal’s reproductive success are rewarded and/or reinforced by positive emotions, while behaviours with fitness-impairing consequences are discouraged with negative emotions This perspective holds that drugs of abuse subvert natural reward circuits by creating a signal in the brain falsely indicating the arrival of a huge fitness benefit (positive reinforcement), and by blocking painful feelings or affect states, ‘short circuiting’ the adaptive functions of negative emotions (Nesse & Berridge 1997). This current evolutionary interpretation of brain function and reward could potentially resolve the paradox, but carries with it several assumptions with which we intend to take issue. We see no obvious resolution to the paradox, we conclude by sketching some possibilities, including a consideration of the potential adaptive outcomes of an evolutionary exposure to plant neurotoxins in humans

ACUTE DRUG REWARD

PLANT CHEMICAL PUNISHMENT OF HERBIVORES

POTENTIAL RESOLUTIONS OF THE PARADOX

Findings

CONCLUSION