Predisposition to Addiction Found in Cocaine Study

[Each Hit]

http://sciam.com/article.cfm?chanID=...F85020F2B25647

March 01, 2007

Predisposition to Addiction Found in Cocaine Study
A lack of dopamine receptors in a specific brain region could trigger increased compulsions, such as drug addiction
By Nikhil Swaminathan



Image: © ISTOCKPHOTO/CHRISTOPHER O'DRISCOLL

RECEPTOR CONNECTOR: A new study finds that a lack of a certain receptor in
the midbrain correlates with both increased impulsivity as well as addictive behavior.


A new study shows that brain circuitry makes some people more susceptible to becoming addicts. Researchers found that a pocket near the top of the brain stem may be key in determining whether someone is likely to engage in compulsive behavior or become hooked on drugs like cocaine, which is currently abused by an estimated two million Americans. The finding could help prevent addiction by predicting those predisposed to such behavior and could also lead to new ways to treat it.

Researchers at the University of Cambridge report in this week's Science that a lower number of specific types of receptors that bind the neurotransmitter dopamine—a chemical central to the brain's reward system—in the front (or ventral) section of the striatum (a midbrain region implicated in planning and movement as well as executive function) correlates to increased impulsive behavior in rats. In addition, they found that the more impulsive animals, when given the option, consumed more cocaine than the calmer rats did.

"Our data provide a link between impulsivity and compulsivity," says lead author Jeffrey Dalley, an experimental psychologist at Cambridge's Behavioral and Clinical Neuroscience Institute. "We have formulated a strong working hypothesis that dopamine dysfunction in the ventral striatum mediates impulsivity and encourages increased intake of cocaine. Increasing use of cocaine eventually affects the entire striatum, including the dorsal [or hind section of the] striatum, which is heavily implicated in compulsive habit-based learning."

At the outset of the experiment, the researchers tested the visual attention and anticipatory behavior of rats, and segregated the most impulsive animals. They then gave six impulsive rats, along with six laid-back ones PET (positron emission tomography) scans that focused on the striatum. The scientists specifically probed the nucleus accumbens, a ventral (front) section of the striatum associated with pleasure processing, to determine the number of D2 dopamine receptors there. (Previous studies have shown a dip in the number of the D2 family of dopamine receptors in cocaine-addicted monkeys.) The Cambridge team found that impulsive rats had 10 percent fewer receptors in their ventral striatum. Next, the rats were hooked up to a catheter and allowed to self-administer cocaine. (This is typically done by the rat depressing a lever.) Researchers observed that all of the rats consumed some amount of the drug, but that the impulsive ones consumed it at twice the rate of the normal (or less impulsive) animals

The findings suggest that a lack of D2-family receptors may predict both the risk of anticipatory impulsivity as well as a predisposition to behaviors like drug and other addictions such as compulsive gambling and shopping. "This is probably one of several 'vulnerability' markers, for future drug addiction," Dalley says. "What determines the final 'tipping' point is obviously very complex—[involving] genes and environment, etc."

Steven Grant, a researcher at the National Institute on Drug Abuse, says that the new findings will help untangle a "chicken and egg problem" with human addiction studies: Previous research found a correlation between the D2-family receptors and drug abuse, but it was unclear whether fewer receptors contributed to addiction or if chronic drug use led to a drop in the number of receptors. "This allows us a framework to interpret the human studies," says Grant.

Diana Martinez, a research psychiatrist at the Columbia University Medical Center, disagrees that the study has direct human implications. "We have done the same study in actual cocaine dependent subjects and we have seen no predictive value of D2/3 receptor binding potential," she says. Martinez adds that, "lower quantities of these receptors have also been reported in a number of human traits that are not generally associated with impulsivity: social phobia, obsessive-compulsive disorder, social detachment and increased age."

The real value of the new research may be that these receptors can provide new and more effective therapies for current addicts, says Michael Nader, a physiologist and pharmacologist at the Wake Forest University School of Medicine in Winston-Salem, N.C. "This identifies a target," he says. "If you have low D2 levels you're more vulnerable; if you change the environment, you can increase those levels." He suggests that treatments that stimulate production of D2 receptors could be beneficial.

"Most licensed treatments are substitution therapies"—such as methadone in the case of heroin addiction—"so they maintain the addicted state, but more safely," says Dalley. "We feel that newer treatments should aim to prevent relapse." He notes that the behavior of the impulsive study rats normalized after they went through withdrawal from cocaine. "The potential here," he says, "is [in] treatments that retard the return of impulsivity in post-cocaine addicts, [which] may be an important contributor to relapse."

[bcubed]

This seems to be a scientifically way of saying, "people differ."

Plenty of people drink moderately, whenever they want to, and have no desire to increase dosage or frequency. Others drink "too much" (who's def?) but basically keep it together. Others completely phuck up their lives.

Some drugs are more addictive than others, but the addictive potential of the user is an undeniable variable.

Hell, some people completely ruin their lives on something like gambling, which involves no outside chemicals at all (though the data's pretty clear that problem gamblers undergo the same sort of nerotransmitter responses that addicts do, too.)

Of course, a completely non-addictive person would have pitifully low experiences of pleasure for anything, and thus, little drive to do anything, be it addictive or beneficial. Probably not very valuable to anyone. (LOL think of the two Kirks )

[stoneinfocus]

You can´t say an addiction would be necessary to feel joy, that´s the opposite of your elaborated opinion in your post.

If some need to have drugs to feel the same joy in life than others do without and this is a physical and hereditary issue, as well as a undenieable success story of mother natures multitude of phenotypes, then we have no right in
judging them or denying the use of their habit for themselves.

When a non-addictice phenyotype has no understanding in the needs of others and is judging and discrediting them, he might be given a lesson in tolerance.

[Nicaine]

Funny, SWIM has never been the impulsive type -- in fact he's the over-cautious type, except when it comes to dopaminergic substances. He knows someone else who uses lots of coke and is EXTREMELY cautious/nonambitious, as well as having anxiety disorder. So much for hypotheses...

Edit -- SWIM suspects they may eventually discover that both impulsive/ambitious and over-cautious types gravitate toward cocaine, and it's the middle-of-the-road folks who don't. The error is in looking at things with biochemical blinders on, i.e. not taking into account the complexity of human behavior.

[stoneinfocus]

there´re many ratios that have to be important, betweeen the catecholamines et al., like it is with the hormones.

So maybe the active/impulsive phenotype might benefit from simply an altered ratio of -say noradrenaline to dopamine, or a down-regulation of a receptors or upregulation, induced by e.g. cocaine (remember ads(h)?), it´s all a close guess, at best, but it works and this has always been the case in the medicine of neuroendocrinology.

Nicaine, could you elaborate what a lack of dopamine has to do with anxiety and impulsiveness?

As I see it, this study is dedicated to those, which simply try to get their dopamine by drugs, because they´re lacking it naturally.

So maybe an impusive or brave behaviour that ought to get a reward, is sought after by cocaine-use, if it doesn´t and vice versa, a anxious, depressed feeling could be elevated or eliminated, by the rise of dopamine and
alleviated by the simulation or stimualtion,or both, of an drug-induced altered state of mind.

And this simply is the principle of various anti-depressant medication and analeptics, which in fact is nearly the same, everyone saying differnt is bullshitting.

[Donmeka]

well SWIM has bad anxiety and kinda of a ocd, like he worries and is too self conscious all the time. when he does cocaine (good cocaine) he feels great a nice high but really just happy and calm, then since he does only small amount his comedown is never bad or nearly unbearable.

SWIM truely believes hes always had a below average level of dopamine in his system, SWIM would take OxyContins but never like his peers insufflating half an 80 or a whole or MORE 0_o small doses would make SWIM feel happy and normal to where he could go on his day. but thats another thread and another tale of SWIMs adventures.


totally agree it depends on te person, theres so many of us that are so different for a reason p