NOTE: THIS ESSAY IS NOT YET COMPLETE

xAddictionbNEUROTRANSMITTERS, NEURONS, AND NEURAL IMPULSES DISCUSSED DURING CLASS (2/14/06). ADD SECTION ON THIS FOR FUTURE SEMESTERS.

Dopamine was originally thought to serve as a kind of pleasure signal in the brain, telling us when something feels good or rewarding. But scientists now believe that dopamine is more a predictor of salience[∂] — that is, it tells us, and then helps us to remember, what we should focus on. When you see a person you are strongly attracted to, scientists can now see a spike of dopamine in your brain. If you are hungry and smell a food you like, dopamine also increases. But even unpleasant experiences — like physical pain or the fear of an intruder in the house — can cause a dopamine spike. (Denizet-Lewis, 2006)

Stimulant drugs, such as cocaine and methamphetamine, cause dopamine-containing neurons to release greater amounts of the neurotransmitter, which activates the reward center described earlier and leads to euphoria[∂]. The nervous system, however, is constructed in such a way that, when its normal activity is disturbed (by drugs, for example), it changes in ways that "try" to reattain normal activity. This process is known as compensation, and is dependent on the plasticity of the nervous system. It can do this in many ways, such as the following:

With regular, repeated "addictive" drug use, ... the brain eventually responds by reducing its normal release of dopamine. Studies also show a simultaneous decrease in the number of dopamine receptors created. That, in turn, makes the brain's reward system less likely to respond to behaviors (romance, a good meal, the company of friends) that produce a normal dopamine surge. The addicted brain essentially becomes pathologically selective, dependent on bigger and bigger blasts of, say, cocaine to feel rewarded. (Denizet-Lewis, 2006)

Compensation, therefore, leads to dependency (DEFINE) and tolerance (DEFINE).

When people addicted to a drug experience situations that remind them of the drug — such as seeing drug paraphenalia — they experience surges of dopamine to parts of the brain related to learning (see Section 3) and the initiation of actions, which causes not a feeling of euphoria but an intense craving for the drug (Volkow, et al., 2006). The amygdala is involved in this: it is important for the learning of behaviors associated with strong emotions, such as the emotions linked to drug intoxication. The craving is what drives most recovering addicts back to drug use. If the craving could be reduced or eliminated, recovering addicts would have a much better chance of abstaining from the drug completely. This is where much research now is focused.

FROM VOLKOW, ET, AL: We measured changes in dopamine by comparing the specific binding of [11C]raclopride when subjects watched a neutral video (nature scenes) versus when they watched a cocaine-cue video (scenes of subjects smoking cocaine). The specific binding of [11C]raclopride in dorsal (caudate and putamen) but not in ventral striatum (in which nucleus accumbens is located) was significantly reduced in the cocaine-cue condition and the magnitude of this reduction correlated with self-reports of craving. Moreover, subjects with the highest scores on measures of withdrawal symptoms and of addiction severity that have been shown to predict treatment outcomes, had the largest dopamine changes in dorsal striatum. This provides evidence that dopamine in the dorsal striatum (region implicated in habit learning and in action initiation) is involved with craving and is a fundamental component of addiction.

FROM Denizet-Lewis, 2006: Dopamine may also make some people more vulnerable to addiction. Recent studies in both animals and humans have indicated that those with low levels of dopamine D2 receptors, which regulate the release of dopamine in the brain, are more likely to find the experience of taking drugs pleasurable. Some researchers, like Volkow, suggest that people with fewer D2 receptors experience a less intense reward signal, causing them to overindulge in order to feel satisfied. In one experiment, Volkow increased the level of dopamine D2 receptors in rats that had low levels. After the increase, the rats significantly curtailed their intake of alcohol, which they had eagerly gulped down before. Unfortunately, we don't yet know how to safely increase the number of dopamine D2 receptors in humans.

GABA--inhibitory neurotransmitter
Glutamate--excitatory neurotransmitter

FROM Denizet-Lewis, 2006: GABA (gamma-aminobutyric acid) is the brain's major inhibitory transmitter, and its role, in essence, is to keep glutamate, the main excitatory transmitter, from overwhelming us. In the extreme, too much glutamate can cause a seizure and too much GABA can put us in a coma. Researchers are particularly interested in the brain's critical balance of GABA and glutamate — some hypothesize that addictive craving is the result of too much glutamate or too little GABA. "We've been able to measure GABA in living brains for some time, but measuring glutamate in living human brains has just become feasible in the last few months," says Frank Vocci, the director of the division on pharmacotherapies and medical consequences at the institute on drug abuse. "What's been shown is that people with alcohol and cocaine problems have less GABA in their brains, and we do know that medications that increase GABA have shown some efficacy in treating addiction." (Vocci says that it isn't yet clear whether the absence of GABA is a cause of addiction or a result.)

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