A “Kindling” Model of the Development of Addiction

Sometimes, while daydreaming in the shower or in the car, an insight hits you out of the blue. That happened last week. It occurred to me that the best neurobiological model of addiction has a serious missing link. Addiction develops. It grows. A successful theory of addiction needs to be a developmental theory – a theory of neural development.

In my view, the neural basis of addiction is best captured by Berridge and Robinson’s model of incentive sensitization. In a nutshell, these researchers show that “wanting” and “liking” are quite independent, subserved by different neurochemicals, and addiction is characterized by “wanting,” not “liking.” That helps explain why addicts keep on craving – and obtaining – their substance of choice long after it stops being pleasureful. The research supporting the model shows that, contrary to a tenacious myth, dopamine does not cause pleasure. Rather, dopamine is critical for the pursuit of goals, including the behaviors required to reach them and – most important– the powerful motivations needed to execute those behaviors. According to Berridge and colleagues, dopamine gets released from the midbrain in buckets when addicts are presented with cues associated with their substance of choice. A sight, sound, or memory, reminiscent of that stuff (e.g., a cramp in the gut, the fleeting glimpse of someone who looks like a drug buddy, a scrap of paper dotted with a few flecks of white powder) will activate dopamine release and send it straight to the nucleus accumbens (NAcc; a major component of the ventral striatum) where it induces goal-oriented behavior (when the stuff is available) or craving (when it’s not).  But the power of cues to elicit the addictive impulse must take time to develop. It’s not present the first time you try drugs or booze, or even necessarily the 20th time. This process is therefore called incentive sensitization; because the cues that trigger drug seeking become sensitized over time.

The trouble is, Berridge and colleagues don’t explain how this sensitization takes hold. The cues must be processed somewhere in the back half of your brain (where “perception” first arises) and they must activate the amygdala, the famous limbic structure that produces emotional feelings on the basis of perception. But how do these perceptual and evaluative processes come to trigger the urge, the thrust, the powerful desire that is the essence of approach motivation? That would have to take place in the frontal cortex and its master motivator, the striatum.

I’d been reading a recent chapter by Berridge and Robinson (2011), in preparation for a class I’d soon be teaching on the neuroscience of addiction. But the paper seemed to be missing something – a mechanism. This bothered me for a few days, and then, out of the blue, I remembered the idea of “kindling” – something I’d read about years before. Kindling in neuropsychology initially meant the tendency for animals to get seizures more and more predictably in response to less and less of the seizure-inducing stimulus. So rats might go into a seizure when exposed to an electric shock, but the amount of electricity needed to evoke the seizure would diminish, session after session, and seizures would eventually occur spontaneously, without any shock.

The kindling model was used at first to understand epileptic seizures, which occur more frequently, with less to trigger them, as people age. But in 1992, Robert Post published a kindling model of depression.  According to Post, depressive episodes follow the same developmental trajectory as epilepsy. An initial depressive episode is triggered by a major stressor, but subsequent bouts of depression are triggered by less and less adversity. That’s why adult depressives get, um, depressed….so easily. In his excellent book, Listening to Prozac, Peter Kramer fleshes out the kindling model of depression. He tells of patients who become more vulnerable to depression with age, despite increasingly minor triggers, as exemplified by a concentration camp survivor whose depression, initially elicited by a horrible experience in his youth, came back to haunt him later in life. More recent work uses the kindling concept to describe the development of bipolar disorder and PTSD. What all these accounts have in common is the notion that sensitivity to certain cues – cues that elicit negative effects or negative affects – increases with development.

Could that be what’s going on in addiction? Could kindling explain incentive sensitization? It could, but so far kindling models have only been applied to the elicitation of negative thoughts, moods, and emotions. Can kindling also apply to the elicitation of actions? Impulsive or compulsive actions like acquiring drugs, gambling away the down payment on your house, or drinking yourself out of your marriage or your job? Instead of taking place in the back half of the brain or the amygdala, kindling would have to arise in the frontal brain, the goal-seeking part, and in particular the ventral striatum or NAcc, the seat of motivated action.

That was the thought that came unbidden last week. Hadn’t I read about kindling in the striatum – somewhere? I went to my computer, and the first paper I looked up was a little-known chapter by Don Tucker — Tucker, D. M. (2001). Motivated anatomy: a core-and-shell model of corticolimbic architecture. Handbook of Neuropsychology, 2nd  Edition, Volume 5, Gainotti (Ed.). Elsevier. All I remembered was that the chapter had knocked me out when I first read it, and Tucker has long been one of my favorite brain theorists. I hit the jackpot! In previous work, Tucker had explained how depression could indeed be kindled in the limbic system – most probably in the amygdala. After all, it’s the amygdala’s job to get sensitized, so that stimuli evoke immediate emotional responses based on previous associations. But in this chapter, Tucker went on to describe kindling in the striatum, the source of voluntary behavior.

So, here’s how it might work: The amygdala, which lies at the gateway of perception, gets sensitized by stimuli. As an addict, you get more and more moved by drug-related cues – the empty pill bottle, the email address of your dealer, the buzzing neon sign in front of the liquor store. And the NAcc gets more and more sensitized to a specific goal – getting the substance or doing the activity — and to the series of moves you can make, you must make, to achieve that goal. Sure enough, there’s a dense pathway of axons leading from the amygdala to the striatum, a one-way street from biased perception to biased action.  So incentive sensitization can take place within and between these two systems, both of which are highly programmable, plastic, modifiable, and loaded with synapses that get molded by experience. Both the amygdala and the striatum serve as hubs at the center of extensive cortical systems. Together they form a macrosystem sometimes referred to as the extended amygdala.  The shaping of synaptic networks within this region may be the mechanism by which meaningful perceptions and meaningful actions converge over development, thereby colonizing one’s emotional memory and cementing one’s emotional habits.

I see addiction as developing in exactly that way. The difference from “normal” development is that the kindling that leads to addiction is focused on goals that are so desirable, so very attractive, that they set in motion a feedback loop between “wanting” and doing. Then, other goals become less and less salient, and that’s a serious problem.



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