Explaining human recreational use of 'pesticides': The neurotoxin regulation model of substance use vs. the hijack model and implications for age and sex differences in drug consumption

Abstract

Most globally popular drugs are plant neurotoxins or their close chemical analogs. These compounds evolved to deter, not reward or reinforce, consumption. Moreover, they reliably activate virtually all toxin defense mechanisms, and are thus correctly identified by human neurophysiology as toxins. Acute drug toxicity must therefore play a more central role in drug use theory. We accordingly challenge the popular idea that the rewarding and reinforcing properties of drugs "hijack" the brain, and propose instead that the brain evolved to carefully regulate neurotoxin consumption to minimize fitness costs and maximize fitness benefits. This perspective provides a compelling explanation for the dramatic changes in substance use that occur during the transition from childhood to adulthood, and for pervasive sex differences in substance use: because nicotine and many other plant neurotoxins are teratogenic, children, and to a lesser extent women of childbearing age, evolved to avoid ingesting them. However, during the course of human evolution many adolescents and adults reaped net benefits from regulated intake of plant neurotoxins. The mesolimbic dopamine system (MDS)1 plays a key, though still not fully understood, role in the ability of laboratory animals to learn an association between a stimulus, such as a tone, and a natural reward, such as sugar water, and to approach and consume the reward (1-6). Drugs of abuse have neurobiological and behavioral effects that closely resemble the effects of sugar and other natural rewards, activating the MDS and producing approach and consummatory behavior, positive feelings, and the learning of cues that predict drug availability. Drugs are rewards (7). Moreover, drugs and sugar are chemically similar: both are small organic molecules that act as ligands for various receptors. In fact, fermentation converts 1 glucose molecule into 2 ethanol molecules (and 2 CO2 molecules), and ethanol contains more calories per gram than glucose (7 vs. 4), underscoring the comparability of a natural reward and a drug. On what basis, then, do neurobiologists classify drug reward as abnormal and food reward as normal? © 2013 Hagen, Roulette and Sullivan.