June 04, 2006
Genetically Engineered Mice Do Not Get Cocaine High

Genetic engineering might one day prevent drug abuse.

COLUMBUS , Ohio – Researchers found that they could eliminate the rewarding effect of cocaine on mice by genetically manipulating a key target of the drug in the animal's brain.

While the researchers aren't suggesting that these genetic modifications be made in humans, the work brings to light the key protein that controls cocaine's effects in the body, which may help scientists develop medications that achieve the same results and therefore help addicts overcome their dependence.

Humans are not evolutionarily adapted to handle recreational drugs. But some day with genetic engineering our offspring might be adapted to resist drug and alcohol abuse.

Howard Gu and colleagues at Ohio State University showed they could genetically engineer mice to be resistant to the effects of cocaine.

He and his colleagues raised laboratory mice with genetic alterations in the gene that codes for the dopamine transporter.

“By doing so we created a dopamine transporter that resists cocaine but also retains its function of taking up dopamine and carrying it back to the neurons,” Gu said.

I am not surprised that an alteraton of a brain protein could produce a different reaction to a drug will at the same time retaining normal function. But what is amazing is that these scientists - using 2006 biotechnology - were able to find an alteration that produces this outcome.

The behavior of the mice with genetically engineered dopamine transporters suggest that they did not get a high off of cocaine

“The normal mice spent more time in the compartment where they had received the cocaine injections,” Gu said. “These animals were seeking more cocaine. However, the mice with the modified transporters showed no preference for either test compartment within the box.”

The researchers used the video footage to measure each animal's activity level after a cocaine injection. The normal mice on cocaine covered roughly five times the distance than the control mice injected with saline (6 meters vs. 1 meter). In contrast, the cocaine-injected mice with the modified dopamine receptors covered about half the distance that the saline-only injected mice covered (roughly 1.5 meters vs. 3 meters.)

“After the cocaine injections, the normal mice ran all over the place, sniffing and checking everything out in the box over and over again, until we took them out of the box,” Gu said. “But cocaine seemed to calm the modified mice, as they sat in a corner for long periods of time.”

“To the modified mice, cocaine appears to be a suppressant, not a stimulant,” Gu said.

Some people argue it will be hard to discover new ways to enhance cognitive function. But using today's biotechnology these Ohio State scientists found a way to reduce the ability of a drug to alter cognitive function. Imagine what tools will be available 20 years from now to use to search for ways to alter functionality in brain proteins.

Share |      Randall Parker, 2006 June 04 10:46 PM  Brain Addiction

Nada said at June 5, 2006 10:13 AM:

Randall Parker wrote:

"Humans are not evolutionarily adapted to handle recreational drugs."

While I can't prove that one way or the other, it does seem to be an extraordinary generalization.

As I recall from reading over the years, only about 10% to 15% of users of any drug commonly accepted as a "recreational drug" actually become addicted. This includes illegal as well as legal recreational drugs.

I think it is an arguable inference to say that the 10-15% are not "evolutionarily adapted to handle recreational drugs". But the other 85-90% equally arguably are so adapted.

Lono said at June 5, 2006 10:42 AM:

Nada - Agreed!

It is normal for any sentient being to desire to manipulate their environment, both internal AND external, for their own benefit.

This is not something that can be genetically engineered out of us, as if it is some kind of disease.

Eventually superior chemical engineering will enable people to use designer "drugs" that will allow us to alter our perception without physical addiction or cellular damage.

Psychological addiction will, of course, always be an issue, but such controversies will belong more to the realm of philosophy than medicine in the near future.

Garson Poole said at June 6, 2006 3:25 PM:

Randall Parker said “some day with genetic engineering our offspring might be adapted to resist drug and alcohol abuse.” This probably will be feasible in the future, but concurrently the methods for hedonic self-manipulation will also be changing. Psychogenic substances that are currently in wide use such as alcohol, marijuana, cocaine, and heroin are absurdly crude in effect and affect. Ingesting or injecting a substance and then relying on generalized diffusion across membranes will elicit laughter in future connoisseurs of pleasure.

Imagine manipulating the brain by using electromagnetic stimulation with very fine precision and neurochemicals with exact targeting. ">http://www.hedweb.com/hedethic/tabconhi.htm"> Pleasure and happiness are among the most important drivers of a market. Hence, entrepreneurs and marketers will try to sell them in multifarious ways using the latest science and technology.

Parents may try to “protect” offspring from dissolute lifestyles with counter measures aimed against alcohol and drugs but children intent on becoming derelicts will easily find superior mental-munitions in the future underground markets.

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