Dopamine Not About Pleasure (Anymore)

To John Salamone, professor of psychology and longtime researcher of the brain chemical dopamine, scientific research can be very slow-moving.

“It takes a long time for things to change in science,” he says. “It’s like pulling on the steering wheel of an ocean liner, then waiting for the huge ship to slowly turn.”

Salamone has spent most of his career battling a particular long-held scientific idea: the popular notion that high levels of brain dopamine are related to experiences of pleasure. As increasing numbers of studies show, he says, the famous neurotransmitter is not responsible for pleasure, but has to do with motivation.

He summarizes and comments on the evidence for this shift in thinking in a Nov. 8 review in the Cell Press journal Neuron.

Methamphetamine vaccine shows promise

Methamphetamine is one of the most addictive and thus commonly-used street drugs – according to the United Nations Office on Drugs and Crime, there are currently nearly 25 million meth addicts worldwide. Help may be on the way, however. Scientists from The Scripps Research Institute have had success in using a methamphetamine vaccine to block the effects on meth on lab rats.

The vaccine works by allowing the body’s immune system to attack methamphetamine molecules in the bloodstream, keeping them from entering the nervous system. This keeps the meth from affecting the user’s brain, and thus removes the incentive for using the drug.

Ordinarily, meth molecules are too small to evoke an antibody response from the body. The vaccine, known as M6, gets around this by linking a meth-related chemical to a larger carrier molecule that does cause an antibody response. Once the antibodies are in the bloodstream, they attack both the carrier molecules and the actual meth molecules.

In tests on rats, M6 blocked two of the typical effects of the drug – loss of the ability to regulate body temperature, and in increase in physical activity. In another ongoing Scripps study, meth-targeting antibodies were grown in cultured cells in a lab, then injected into rats in a concentrated dose. This approach also blocked the effects of the drug.

More animal trials are planned for now, with the possibility of human trials occurring in the future.

Researchers Find That Diabetes Drug Could Be Effective in Treating Addiction

Vanderbilt researchers are reporting today that a drug currently used to treat type 2 diabetes could be just as effective in treating addiction to drugs, including cocaine.

The findings, published online as a Letter To The Editor in the journal Molecular Psychiatry, could have far-reaching implications for patients worldwide who suffer from addiction.

“What we have demonstrated is that a brain mechanism already known to be therapeutic for the treatment of diabetes also appears to be implicated in at least certain types of drug addiction,” said Gregg Stanwood, Ph.D., assistant professor of Pharmacology and an investigator within the Vanderbilt Kennedy Center and Vanderbilt Brain Institute.

“We found that this drug called Exendin-4 that is already used for the medical management of diabetes, reduces the rewarding effects of cocaine in animals. We suspect that this is a general mechanism that will translate to additional drugs of abuse, especially other stimulants like amphetamine and methamphetamine.”

Co-author Aurelio Galli, Ph.D., professor of Molecular Physiology and Biophysics and Vanderbilt Brain Institute investigator, said Exendin-4 is already FDA-approved for diabetes (Byetta and Bydureon), so this target isn’t just “druggable” – it’s already “drugged.”

“I think the power of this research is that it is so easily translatable to humans because it is already FDA approved,” said Galli, also co-director of the Neuroscience Program in Substance Abuse (N-PISA) at Vanderbilt University. “This is the first indication that it will work on psychostimulants. So our studies offer immediate translational opportunities to improve outcomes in human abusers.”

Does motherhood dampen cocaine’s effects?

Mother rats respond much differently to cocaine than female rats that have never given birth, according to new University of Michigan research that looks at both behavior and brain chemistry.

The findings may help lay the groundwork for more tailored human addiction treatment, based on scientific understanding of how gender, hormones and life experience impact drug use.

In an oral presentation at the Society for Neuroscience meeting, U-M researcher Jennifer Cummings, Ph.D., summarized findings from experiments with rats at the Molecular and Behavioral Neuroscience Institute, part of the U-M Medical School. She worked with Jill Becker, Ph.D., of the U-M Department of Psychology.

They identified clear differences in how intensely the “pleasure centers” in the mother rats’ brains reacted to the drug, compared with non-mothers. Mother rats’ brains released less of a chemical called dopamine, which helps cause the “high” from cocaine.

They also found an interaction with stress: mother rats that were exposed to periods of increased stress weren’t willing to work as hard to get a dose of cocaine, compared with rats that had never given birth or mother rats that weren’t exposed to the stress – even though the stressed mother rats showed an increased tendency to use cocaine when it was easy to get.

Taken together, the findings suggest that the experience of becoming a mother alters a female’s overall response to cocaine – adding complexity to the issue of how best to treat addiction.

“While we have not yet identified a mechanism to explain these differences, they do suggest that the reward system and brain circuitry affected by cocaine is changed with maternal experience,” says Cummings, a research investigator at MBNI and former postdoctoral fellow in Becker’s laboratory. “The next step is to determine how factors such as hormone changes in pregnancy and early motherhood, and the experience of caring for offspring, might be differentially contributing to this response.”

Relapse or recovery? Neuroimaging predicts course of substance addiction treatment

An Indiana University study has provided preliminary evidence that by measuring brain activity through the use of neuroimaging, researchers can predict who is likely to have an easier time getting off drugs and alcohol, and who will need extra help.

"We can also see how brain activity changes as people recover from their addictions," said Joshua Brown, assistant professor in the Department of Psychological and Brain Sciences at Indiana University Bloomington, part of the College of Arts and Sciences.

The chronic occurrence of relapse underscores the need for improved methods of treatment and relapse prevention. One potential cause for relapse is deficient self-regulatory control over behavior and decision-making. Specifically this lack of self-regulatory ability in substance dependent individuals has been associated with dysfunction of a mesolimbic-frontal brain network. Reduced activity within this self-regulatory brain network has previously been implicated in relapse, but the specific relationship between this network, self-regulatory ability and recovery is yet to be determined.

Morphine and cocaine affect reward sensation differently

A new study by scientists in the US has found that the opiate morphine and the stimulant cocaine act on the reward centers in the brain in different ways, contradicting previous theories that these types of drugs acted in the same way.

Morphine and cocaine both affect the flow of the neurotransmitter dopamine, which has been shown to be important in the feeling of reward. When a dopamine neuron is stimulated it releases dopamine, which is then taken up by neighboring cells. Any excess is reabsorbed into the original dopamine neuron by a process known as “reuptake.”

Cocaine is known to block reuptake, and the excess dopamine leads to an enhanced reward effect. Cocaine is also known to make the cells in the nucleus accumbens, which receives signals from the VTA, more sensitive to cocaine. It was already known a protein called brain-derived neurotrophic factor (BDNF) in the VTA region of the brain enhances the reward response to cocaine.

The new study shows that BDNF has the opposite effect when morphine is present, decreasing the reward response and the development of addiction rather than enhancing it. The researchers identified numerous genes regulated by BDNF and associated with its effects. They used genetic techniques to suppress BDNF, and then directly excited the neurons in the nucleus accumbens that normally receives transmitted impulses from the VTA.

They found that suppressing BDNF in the VTA allowed morphine to increase the excitability of dopamine neurons and hence enhance the reward. When they optically excited the dopamine terminals in the nucleus accumbens that normally receive the transmissions from the VTA, they also found a reversal in the normal effect of BDNF.

Have you ever wondered why some people find it so much easier to stop smoking than others?

New research shows that vulnerability to smoking addiction is shaped by our genes. A study from the Montreal Neurological Institute and Hospital - The Neuro, McGill University shows that people with genetically fast nicotine metabolism have a significantly greater brain response to smoking cues than those with slow nicotine metabolism. Previous research shows that greater reactivity to smoking cues predicts decreased success at smoking cessation and that environmental cues promote increased nicotine intake in animals and humans. This new finding that nicotine metabolism rates affect the brain’s response to smoking may lead the way for tailoring smoking cessation programs based on individual genetics.