Cocaine "highs" in mice can be genetically manipulated - keyway to better control of addicts ?

Howard Gu, associate professor of pharmacology and psychiatry at Ohio State University and colleagues at the University of Tennessee College of Medicine, in Memphis, and Yale University have reported (May 29 in the Proceedings of the National Academy of Sciences.) 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.

This appears to confirm that the dopamine transporter – a protein that moves the neurotransmitter dopamine from outside a neuron into the inside of the cell – is a prime target for developing drugs to fight cocaine addiction.

“Cocaine blocks dopamine transporters, and this action ultimately is what makes a person feel high,” Gu said. “We found that cocaine would not produce a high if it could not block the transporters.”

How do you tell if a mouse his "high" on Columbian Marching Powder ? Well Gu and his coleagues videoed the effects of twin batches of mice normal / genetically modified, and untimately determined that restless activity and more and lengthy journeys indicated that such mice were not affected by cocaine and that passivity meant the mice were "high".

“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.

This raises the possibility of finding compounds that could produce the same effect that the genetic modifications did in this study. “We hope to find certain drugs that prevent cocaine from binding to transporters, but that still allow the transporter protein to carry the dopamine back to the neuron,” he said.

So we need to find a drug to prevent the action of another drug that develops a huge and immensely profitable world wide industry.....

The researchers received grants for this work from the National Institute on Drug Abuse, the National Institute of Mental Health and the National Alliance for Research on Schizophrenia and Depression.

Technical note

Dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) are well known as high affinity targets for the psycho-stimulants cocaine and amphetamines in humans. The transporters are also molecular targets for successful therapeutic drugs, such as Ritalin (methylphenidate), Tofranil (imipramine), Prozac (fluoxetine), Zoloft (Sertraline), Luvox (fluvoxamine), Paxil (paroxetine), and Wellbutrin (bupropion). These drugs are used to treat several neurological and mental disorders, including attention-deficit/hyperactivity disorder, depression, anxiety, Autism, obsessive-compulsive disorder, and minimal brain dysfunction.

Cocaine resistant caterpillars as biological pest controllers ?
Cocaine is produced by coca plants as a chemical defense to deter feeding by insects. It has been shown that cocaine sprayed on tomato leaves reduces insect feeding, causes abnormal behaviors at low doses and kills feeding insects at doses equivalent to that in coca leaves [Nathanson, J.A., Hunnicutt, E.J., Kantham, L., Scavone, C., 1993. Cocaine as a naturally occurring insecticide. Proc. Natl. Acad. Sci. U. S. A. 90, 9645-9648.].

Most insects avoid coca leaves except the larvae of a large beige moth Eloria noyesi, a caterpillar pest of coca plants, which feeds preferentially on coca leaves. Hu has looked at the gene sequencing but does not feel the same mechanism is at work to provide cocaine tolerance.

It has however been suggested recently by Gonzalo Andrade, a biology professor with Colombia's Universidad Nacional, that this could be a natural way to eradicate the coca plants as a method of biological control. "The larvae of the moth Eloria Noyesi presents the most serious threat to the coca plant. This moth lives through out the coca-growing region of South America and seems to feed almost exclusively on E. coca. It has also been recorded feeding on E. novogranatense in Colombia and northern Peru. The larva will develop in about a month and will eat up to 50 leaves in its lifetime. The larva will also eat the shoots of the bush that grow out after harvest. If Eloria attacks a plant repeatedly, even a strong plant will die."

Ricardo Vargas, director of Andean Action, (Acción Andina) said the moths, which are about twice the size of an average fly, would threaten other species of plants if released by their thousands into the wild.

"With a plan like this, the chance for ecological mischief is very high and very dangerous," Vargas said.