This post is highly technical and drawn from another website that is even MORE technical. Hard as it is to read, I thought it was important because it is so basic to behavior we would like to control: not just DEcrease, but also INcrease.
Addiction is something that happens in the brain of mammals. First there is the lighting up of pleasure centers over food, sex, a substance, something else that’s pleasant, and then something -- repetition? Another brain function? -- converts that into an uncontrollable craving that punishes the body with bad consequences if it isn’t secured. One can become addicted to something painful, destructive, and altogether unpleasant.
Most of the research is about illegal substances. From www.ncbi.nlm.nih.gov Two major lines are pursued: the actual molecules involved and the neurostructures affected.
The stages of addiction are defined as:
(a) compulsion to seek and take the drug,
b) loss of control in limiting intake, and
(c) emergence of a negative emotional state (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented.
Then there is a small cycle within the act of taking the drug:
1. preoccupation/anticipation,
2. binge intoxication,
3. withdrawal/negative affect
These distinctions work for non-physical addictions, such as addiction to love or praise, emotions that affect the complex of the brain both chemically and through nerve action. Defining “reinforcements” that make these into addictions is part of the task of understanding. These can be explored as studies in animals, but not the emotional mechanisms of human beings, which were evolved later, esp. the functions in the pre-frontal cortex. Clearly, addiction is a matter of “operant conditioning” -- the link formed when two things coincide, like Pavlov’s dog hearing a bell ring every time it was fed and finally getting so it salivated if you rang the bell. But until now we haven’t had the ability to detect what happens to the molecules and neurons when two things become associated. You might want to look up the phrases that I colored red: I did.
“. . . animal models of addiction focused on the synaptic sites [the little spaces between the ends of the neuron strands] and transductive mechanisms (how these sites convey changes in excitability [how the signal gets sent across]) in the nervous system on which drugs act initially to produce their positive reinforcing effects.” So the idea seems to be that drugs make the neurons more sensitive and the signal more intense.
Drugs self-administered by animals correspond well with those with high abuse potential in humans, and intravenous drug self-administration is considered an animal model predictive of abuse potential. [If the animal will go get the substance willingly, even if it’s intravenous, then people will do that, too.] Other validated measures of the acute rewarding effects of drugs of abuse include brain stimulation reward and conditioned place preference. [If the drug’s effect on the brain pleasure center shows as strong on brain activity detecting machines and if the animal keeps going to the place where it normally gets the drug, then people will get hooked easily.]
“. . .ingestion of the drug itself, cues associated with the drug, and exposure to stressors.” These are the three factors that make addiction more likely: 1) the process of taking the drug, esp. intravenously which means a little ritual; 2) things like where the drug is taken, with whom (welcoming friends?), what the atmosphere is like (safe, hidden), and 3) whether they are under pressure or in danger some way (beaten up, having to do unpleasant things).
I left the blue Wiki links in for these anatomy names. “Drugs of abuse have been [detected to affect] the origins and terminal areas of the mesocorticolimbic dopamine system” This means the “middle of the connections between the cortex (outer layer) of the brain and limbic system. “ From Wikipedia: “The limbic system includes the olfactory bulbs, hippocampus, amygdala, anterior thalamic nuclei, fornix, column of fornix, mamillary body, septum pellucidum, habenular commisure, cingulate gyrus, parahippocampal gyrus, limbic cortex, limbic midbrain areas and pons. It supports a variety of functions, including emotion, behavior, motivation, long-term memory and olfaction. It appears to be primarily responsible for our emotional life, and has a great deal to do with the formation of memories.” In short, functions of identity and choice.
Specific components of the basal forebrain have more recently been identified with the hedonic [pleasant] neuroadaptations to acute drug reward and have focused on elements of the extended amygdala (Koob, 2003). As the neural circuits for the reinforcing effects of drugs of abuse have evolved, the role of neurotransmitters/neuromodulators also have evolved, and four of those systems are discussed below: mesolimbic dopamine, opioid peptide, gamma-aminobutyric acid (GABA), and serotonin.
Now I’ll summarize a bit. If signaling molecules have been sent through the neurons and then stop, the ability to feel good will go away, even if the addiction has nothing to do with taking drugs. Epinephrine, which signals alarm and danger, will increase. Food tastes bad, hugs are uncomfortable, etc. In fact, the symptoms can be like flu. When the signaling molecules the drugs send through the neurons is returned, it will take MORE to get the same effect of pleasure as before.
“These results suggest not only a change in function of neurotransmitters associated with the acute reinforcing effects of drugs (dopamine, opioid peptides, serotonin, and GABA) during the development of dependence, but also recruitment of the brain arousal and stress systems (glutamate, CRF, and norepinephrine) and dysregulation of the NPY brain anti-stress system. These changes would represent a “between-system” neuroadaptation. Reward mechanisms in dependence are compromised by disruption of neurochemical systems involved in processing natural rewards and by recruitment of the anti-reward systems.” Not only does the high go away without the drugs, but also the body signals all sorts of alarm. The article names the bits of anatomy that do this: a whole complex.
If animals are weaned off drugs and then pushed back into taking them, there are differences in the brain bits that activate to reinstate the addiction. What’s interesting is that when this is done to humans, there is a fourth route of brain response. It is in the most highly evolved part of the brain, behind the forehead, the location of empathy, morality, and self-control. In human imaging studies, another common element of drug dependence is decreased function in the orbitofrontal/medial prefrontal cortex as measured both by neuropsychological tests and imaging. That’s the part of the brain behind the forehead. The same as the part often damaged in a concussion.
So the neurons are running a deficit that’s uncomfortable, molecules that signal distress and anxiety are triggered, every cue associated with taking the drug urges it be taken, and the part of the brain that would ordinarily override urges with rational thought is disabled. Things that would ordinarily be pleasant and comforting have no effect.
Another piece of the puzzle is biosynthesis, which means that opiods (the earliest and most thoroughly studied molecule) are made in the body, with variations in the amounts, sources and impact of them on body function. “All of them are made via three large precursor proteins, called opioimelanocortin, proenkephalin, and prodynorphin. Opiomelanocortin is of particular interest because it is the precursor for several important and seemingly unrelated biologically active molecules, namely, b-endorphin, adrenocorticotropic hormone, and several melanocyte-stimulating hormones.” (Since melanin, the dark pigment in the skin, seems to be involved somehow, I will not be surprised if the reputation of redheads is connected to these molecules, maybe through mutation of specific genes which are now identified, cloned, and studied. So far as I know there are no red-headed lab rats.)
Maybe the most cutting edge studies are the ones trying to find and change genes that don’t code for susceptibility but code for turning those susceptibility genes on and off. The day when an addict can be “vaccinated” in a way that changes his or her essential genetic structure so that addiction is not possible is still over the horizon. But we think it’s there.
The important insight is that addiction is in the addict, the susceptibility of their own biological systems. It is something real, molecular, working at the cell level, inherited, and then triggered by something in the environment. It over-rides rationality and stress due to danger will over-ride resistance. But both something as powerful as sex or as reduced to an empathic second-hand experience as pornography can be addictive. Something as powerful as violence or as reduced to an empathic second-hand experience as violent video gaming can be addictive. Any operant conditioning that connects even an innocent pleasure to these internal molecular and neurological loops can become addictive.
Got time for Starbucks? I love your guitar playing. I need a hug. Human behavior.
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