What Is the Link between Eating, Reproducing, & Addiction?

Abstract

We are wired with the drive to stay alive – with a system that makes it pleasurable for us to eat, to seek shelter, and to reproduce. The problem is that addictive substances can subvert these same processes that were intended to keep us alive and to ensure species survival. This column is the first in a series that will explore the neuroscientific bases of addiction. As a basis for understanding addiction, this article focuses on the brain’s reward system, also known as the pleasure center or motivation system, which is the foundation for life-maintaining but also addictive behaviors. Subsequent articles will explore the influence of genetics, learning, risk and protective factors, stress, and specific neurotransmitters, such as glutamate.As we know, the “reward system” includes key areas or centers, connecting tracts, and several key neurotransmitters. The main areas are the ventral tegmental area (VTA) located in the mid-brain just above the hippocampus and in front of the substantia nigra; the nucleus accumbens (NAc) in the striatum just below the front end of the corpus callosum; and the prefrontal cortex, located just behind the forehead and just in front of the motor areas of the cortex. Some of the other areas involved include the locus coeruleus, the amygdala, the hippocampus, and the insula. The main nerve bundles or tracts that connect these areas are the mesolimbic, mesocortical, and mesostriatal pathways. The main neurotransmitters include dopamine, endogenous opioids, endocannabinoids, serotonin, and glutamate, although it is likely that other neurotransmitters as well as neuropeptides are also involved (Figure 1).The power of the reward system has been revealed in experiments in which experimental animals were found to vigorously continue self-stimulation when electrodes were placed in various locations within the reward-system structures (Olds & Milner, 1954). Esch and Stefano (2004) reviewed the important role of this system both in maintaining health and in addiction. More recently, brain-imaging techniques such as positron emission tomography (PET) scanning have helped us appreciate how addiction itself modifies the function of the brain’s reward system. In research by Volkow and colleagues (2009, 2011), cocaine use in nonaddicted persons resulted in a significant increase in dopamine release in the vicinity of the nucleus accumbens. Both the speed of drug administration, which is a function of the route of administration, and the amount of dopamine subsequently released, were directly related to the “high” experienced by the drug recipient. In cocaine-addicted individuals, however, this response was altered so that the dopamine released in response to cocaine intake was markedly diminished. Instead, there was a marked increase in dopamine in response to conditioning cues – such as seeing a video of another person buying or smoking cocaine. When the stimulus for dopamine release occurred in response to these conditioned cues, the addicted person experienced “craving” for the drug. There was a direct relationship between addiction severity and dopamine release during the viewing of these videos (Volkow et al., 2011).Another recent finding related to addiction is the modulating influence of a variety of stress-related neuropeptides, particularly a corticotropin-releasing factor that has been shown to increase dopamine release in the nucleus accumbens during the development of addictive behaviors (Sinha, 2008). Neuropeptides are brain signaling molecules of fewer than 40 amino acids that can modulate neuronal function in ways that are similar, but not identical, to the actions of neurotransmitters (Burbach, 2011; Logrip et al., 2011). The use of addictive drugs and the associated stress are known to activate the hypothalamic–pituitary–adrenal (HPA) axis, an action that probably has a role in addiction but may have an even greater effect during drug abstinence in addicted persons. Research has shown that the increases in corticotropin-releasing factor that occur during withdrawal are related to the signs and symptoms associated with withdrawal, particularly the anxiety that may contribute to relapse (Shalev et al., 2009; Logrip et al., 2011).Given that we all have brain reward systems, why is it that some of us when exposed to potentially addictive substances develop addictions and others do not? The next column in this series will discuss the relationship between genetics and addiction. Exploring this relationship contributes another piece to understanding the complex puzzle of addiction.This project was funded by the National Institute on Drug Abuse, National Institutes of Health, Award Number R25DA028796. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.