Enzyme might be target for treating smoking, alcoholism at same time

An enzyme that appears to play a role in controlling the brain's response to nicotine and alcohol in mice might be a promising target for a drug that simultaneously would treat nicotine addiction and alcohol abuse in people, according to a study by researchers at the Ernest Gallo Clinic and Research Center, affiliated with the University of California, San Francisco.

Over the course of four weeks, mice genetically engineered to lack the gene for (PKC) epsilon consumed less of a nicotine-containing water solution than normal mice, and were less likely to return to a chamber in which they had been given nicotine.

In contrast, normal mice steadily increased their consumption of nicotine solution while the mice lacking PKC epsilon did not.

The study was conducted by Gallo senior associate director and investigator Robert O. Messing, MD, UCSF professor of neurology, and Gallo researcher Anna M. Lee, PhD.

In normal mice, as in humans, nicotine binds to a certain class of nicotinic receptors located on dopamine neurons, which causes dopamine to be released in the brain. Dopamine creates a feeling of enjoyment, and thus prompts a sense of reward. Lee and Messing found that mice lacking PKC epsilon are deficient in these nicotinic receptors.

The study appears in the online Early Edition of the for the week of September 12, 2011.

The finding complements earlier research in which Messing found that mice genetically engineered to lack the PKC epsilon enzyme drank less alcohol than normal mice and were disinclined to return to a chamber in which they had been given alcohol.

"This could mean that these mice might not get the same sense of reward from nicotine or alcohol," said Messing. "The enzyme looks like it regulates the part of the reward system that involves these ." The reward system is a complex of areas in the brain that affect craving for nicotine, alcohol and other addictive substances.

The next step in the research, said Messing, would be to develop compounds that inhibit epsilon. The ultimate goal, he said, would be medications that could be used "to take the edge off of addiction by helping people get over some of their reward craving."

More information: “Protein kinase C epsilon modulates nicotine consumption and dopamine reward signals in the nucleus accumbens,” by Anna M. Lee and Robert O. Messing, PNAS.

Related Stories

Dissecting the machinery of nicotine's reward

Jun 14, 2006

Understanding what makes people crave the high of nicotine is a key to developing treatment for this highly addictive drug. And that understanding involves tracing the neural machinery by which nicotine switches on the brain's ...

New compounds may treat both alcohol and cigarette addictions

Nov 03, 2010

Researchers at the Ernest Gallo Clinic and Research Center at the University of California, San Francisco, and Pfizer Inc., have determined that two new compounds may be effective in treating both alcohol and nicotine dependence ...

Nicotine triggers the same brain reward circuitry as opiates

Jun 15, 2005

In experiments with mice, researchers have found that nicotine triggers the same neural pathways that give opiates such as heroin their addictively rewarding properties--including associating an environment with the drug's ...

Recommended for you

New malaria vaccine candidates identified

2 hours ago

Researchers have discovered new vaccine targets that could help in the battle against malaria. Taking a new, large-scale approach to this search, researchers tested a library of proteins from the Plasmodium fa ...

User comments