Research News

Dopamine May Play Role in Cue-Induced Craving Distinct from Its Role Regulating Reward Effects

NIDA-supported researchers from Brookhaven National Laboratory and the State University of New York at Stony Brook have found evidence in humans that dopamine plays a role in the conditioned cue response to food. Cues—seeing, smelling, and tasting something enjoyable—increase the desire for the reward without necessarily enhancing the pleasure of the reward itself.

Positron emission tomography (PET) was used to measure changes in dopamine in the brains of 10 healthy adults (eight men and two women) during food and neutral stimulations. Food stimulation consisted of the participants viewing, smelling, and tasting their favorite foods but not actually eating the foods. For neutral stimulation, participants described their family genealogy in detail. Prior to and during food stimulation, participants were instructed to rate their feelings of "hunger," "desire for food," "alertness," "stimulation," and "talkativeness" on a scale of 1 to 10. Participants had fasted 16-20 hours before PET scans were conducted.

Food stimulation caused an increase in dopamine in the dorsal striatum but not in the ventral striatum, where the nucleus accumbens is located. This suggests that dopamine may be involved in food motivation that is distinct from its role in regulating food's reward effects through the nucleus accumbens. Previous research has linked increases in dopamine in the nucleus accumbens, the reward center of the brain, with addiction.

• WHAT IT MEANS: The finding that dopamine may play a role in cue-induced effects could have important implications in drug addiction research. Many individuals addicted to drugs, especially cocaine and nicotine, are susceptible to cue-induced cravings. A better understanding of the biological basis of cue-related behaviors may provide better insights in the development of more effective behavioral and pharmacological treatments for drug addiction.
  

The study was published by lead investigator Dr. Nora Volkow in the electronic online journal, Synapse, and is due to be published in the June 1, 2002 hard-copy issue of Synapse.

Long-Term Cognitive Impairment Found in Crack-Cocaine Abusers

Impaired memory and motor skills were found in crack-cocaine users up to 6 months after their last use of the drug. Individuals with a history of heavy crack use had the most severe impairments. The researchers believe that these deficits are evidence of brain damage caused by substance abuse.

The researchers administered a battery of comprehensive neuropsychological tests to 20 crack-dependent subjects, 37 crack-and-alcohol-dependent subjects, and 29 individuals with no history of drug or alcohol abuse. The tests were given twice–the first time following 6 weeks of abstinence from drugs and again after 6 months of drug abstinence.

The tests assessed the subjects’ attention span, decision-making, spatial processing, immediate and delayed memory, calculation ability, reaction time, verbal fluency, and psychomotor skills.

Both drug-abusing groups showed significant cognitive impairments at both the 6-week and the 6-month time points. The largest effects were found in the executive function and spatial processing assessments.

• WHAT IT MEANS: With approximately 2 million cocaine abusers in the United States, the finding that brain damage resulting in long-term impaired mental and physical functioning can result from its use makes developing and utilizing effective prevention and treatment methods an urgent public health priority.
  

The study was published in the February 2002 issue of Drug and Alcohol Dependence by a research team from Neurobehavioral Research, Inc., Corte Madera, CA; University of Illinois at Chicago; and the Herrick/Alta Bates Hospital, Berkeley, CA. Dr. George Fein was the lead author.

Neuronal Differences in Brain Regions Involved in Decision-Making and Other Functions Observed for the First Time in Chronic Users of Cocaine

Researchers at the University of Pennsylvania have detected differences in areas of the brain in chronic cocaine users. These differences were detected in regions involved in decision making, behavioral inhibition, and emotional reaction to the environment.

Using magnetic resonance imaging (MRI) and other brain mapping techniques, the researchers, led by Dr. Teresa R. Franklin, examined 13 men who had used cocaine for an average of 13 years each. They found that, compared to controls who had never used cocaine, select regions of the brains of the cocaine users had less gray matter. This decrease in critical working brain tissue ranged from 5 to 11 percent. This is the first time in either animal or human studies that differences in gray matter concentrations have been found in chronic cocaine users.

The investigators suggest that some of the behaviors observed in chronic cocaine use– such as choosing immediate gratification over long-term reward; engaging in risky behaviors, particularly when attempting to obtain cocaine; and succumbing to the overwhelming desire to seek and use drugs undeterred by the prospect of future negative consequences– may be a result of these gray matter deficiencies.

• WHAT IT MEANS: Understanding the long-term impact that cocaine can have on the brain and cognition will help scientists to develop strategies to reverse those effects and, and, ultimately, restore the brain to normal function.
  

The study was published in the January, 2002 issue of Biological Psychiatry.

Drug Used in Treatment of Alcoholism May Have Role in the Treatment of HIV

Naltrexone, a drug used in the treatment of heroin addiction and alcoholism, may increase the effectiveness of the antiretroviral drugs zidovudine (AZT) and indinavir, which are used in the treatment of human immunodeficiency virus (HIV). Naltrexone blocks opioid receptors in the brain preventing the “high” associated with the use of heroin and other opioids. Although the mechanism of the synergistic activity of naltrexone, AZT, and indinavir is unknown, the interaction of naltrexone with opioid receptors may play a role.

Researchers at the Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, Hennepin County Medical Center and the University of Minnesota Medical School in Minneapolis conducted an in vitro study with CD4+ T lymphocytes. These cells express opioid receptors and are the primary cells targeted by HIV.

Cells were obtained from the blood of HIV-1-seronegative individuals and then infected with HIV-1. Cells were incubated for 4 days with AZT, indinavir, naltrexone or combinations of the drugs. HIV-1 p24 antigen levels were measured using an enzyme-linked immunoassay. The researchers found that naltrexone alone had no effect on HIV-1 expression by the cells, but when the drug was added to cell cultures containing AZT or indinavir, the antiviral activity of these drugs increased.

• WHAT IT MEANS: Naltrexone is a novel approach to HIV treatment since it appears to target the cells infected with the virus rather than the virus itself, unlike current treatment medications.
  

The study, led by Dr. Phillip Peterson, appears in the November 2001 issue of Drug and Alcohol Dependence.

The National Institute on Drug Abuse is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports more than 85 percent of the world's research on the health aspects of drug abuse and addiction. The Institute carries out a large variety of programs to ensure the rapid dissemination of research information and its implementation in policy and practice. Fact sheets on the health effects of drugs of abuse and further information on NIDA research can be found on the NIDA web site at http://www.drugabuse.gov.