NRSC 2110 Blog

Each year, over half a million Americans die from drug use. In a recent study published in Nature Neuroscience, addiction was defined as "a chronically relapsing disorder characterized by a compulsion to seek and take drugs, a loss of control over intake, and the emergence of a negative emotional state during abstinence." But that's not what addiction is, not really. Addiction is a high-speed chase into the depths of human despair. It's no man's land- black, and empty, and unbearable. And relapse is worse. Relapse is the shadows in the darkest corners of human existence. So wouldn't it be great if there were a cure for this relapse monster? Researchers may have found just that.

In a study published in January (http://www.nature.com/neuro/journal/v14/n4/full/nn.2758.html), researchers studied an area of the brain called the ventromedial prefrontal cortex (vmPFC) and its role in reducing context-induced heroin seeking (because we all know that being in a place where you used to shoot up is just as risky as having the needle poised in your veins). In previous studies on cocaine addiction in rodents, activation of the vmPFC inhibited drug relapse. Bossert et al. challenged this idea by identifying a subpopulation of neurons in the vmPFC that increases context-induced heroin-seeking behavior upon activation.

To identify this population of neurons in the vmPFC, scientists used Fos immunohistochemistry to show that reexposure to an environment associated with heroin consumption activated these neurons. The rats were exposed to two contexts: in context 1, rats were trained to self-administer heroin 3 hours per day for 12 days by pressing on a lever. In context 2 (which differed from context 1 in tactile, visual, auditory, and circadian components), rats could still press a lever, but did not receive heroin. Consequently, they eventually stopped pressing the lever. Following the extinction training, rats were reintroduced to either context 1 or 2 and given lever access, although no heroin was supplied.

The most significant finding was that 71% of the neurons recruited by reexposure to context 1 were excitatory glutamatergic neurons (13% were inhibitory GABA neurons). Thus, reexposure to an environment associated with heroin recruits excitatory pyramidal neurons. Most importantly, these neurons are responsible for the learned association between environmental factors and the effects of heroin.

Bossert et al. then used an innovative method to selectively inactivate vmPFC neurons that were activated in the heroin context. A prodrug called Daun02, which decreases cell excitability for several days, was injected into the vmPFC after reexposure to the heroin context. When exposed to context 1 a second time, rats that received the prodrug immediately following reexposure to the context 1 the first time showed a decrease in context-induced activation of vmPFC neurons, AND diminished heroin-seeking behavior.

So why is this important? Researchers have found a neuron population involved in environmentally triggered relapse, and we now know that this population reacts differently for heroin than it does for cocaine. But how promising is this study in the future of addiction? It's quite obvious that just quitting a drug will never keep you safe from the drug itself. But at least we know which neuron population is responsible for the horrific heroin relapse. So instead of going to the methadone clinic, junkies can just get parts of their ventromedial prefrontal cortex lesioned. And if they're addicted to heroin AND cocaine, well then they're really screwed.

That's what bothers me about addiction studies like these: rather than feeling enlightened and hopeful, I feel discouraged and even more in the dark than I was before I read the study. While it's great that 'our knowledge is expanding in the field of addiction,' the plausibility of expanding this study to humans (which are different from genetically engineered rodents), is slim to none. For all their scientific wisdom, researchers could never accurately convey what addiction is. Relapse can't be scientifically treated, because no matter how many neurons you activate or inactivate, the house on the corner can still kill you. Relapse is the razor's edge between life and death, not the number of lever presses inside a cage.