Animal Brains as the Model for Human Addiciton

The Brookhaven-led studies of GVG, or gamma vinyl-GABA, involved research on the brains of both primates and rodents as stand-ins for the human brain, using ten different biochemical and behavioral techniques.

The team's first publication in 1992 demonstrated that GVG inhibited brain dopamine in rodents, as well as the biochemical effects of cocaine in the region of the brain that is thought to play the most important role in addiction. These studies served as the impetus to pursue GVG further in primates, and to look at its role in cocaine-related behavior.

The primate studies reported for cocaine and nicotine used a sophisticated medical imaging technique called PET, for positron emission tomography. PET scans are made using a large donut-shaped "camera," which records faint signals from short-lived radioactive isotopes injected into the body. PET is used in hospitals and scientific institutions throughout the world for research and diagnosis. BNL researchers have used PET scans for decades to study the brain, and have made many discoveries pertaining to addiction, aging, mental illness and normal brain function.

For the nicotine and cocaine studies in Synapse, the researchers looked at the brain scans of primates before and after they had taken nicotine or cocaine. The primates that had been given a dose of GVG before their nicotine or cocaine dose showed normal levels of dopamine in the brain, compared with those that had not gotten GVG. The primates are part of a resident group housed at BNL in facilities accredited by the Association for the Assessment and Accreditation of Laboratory Animal Care (AAALAC).

Other methods used to evaluate GVG's effects involved rodents. For example, researchers at St. John's University and Boston University gave rats nicotine or cocaine repeatedly in order to examine their behavior when they received GVG. They also looked at the rats' tendency to return to a place where they had gotten nicotine or cocaine previously.

Called conditioned place preference, or CPP, this behavior is also important in human nicotine and cocaine addiction. Recovering addicts often fall back into addiction if they are exposed to stimuli that they associate with their former use of the drug; for example, drug paraphernalia or an alley or house where they routinely bought or used drugs.

Biochemical Studies

Direct measurement of brain dopamine levels (Microdialysis)
Medical imaging of brain dopamine receptor activity (Positron emission tomography)
Metabolism and drug-delivery studies (Positron emission tomography) cocaine study only
Effect of cocaine-GVG combination on heart function (synergistic drug-drug interaction) cocaine study only

Behavioral Studies

Bar-pressing for cocaine, same number of presses each time (Fixed-ratio cocaine self-administration) cocaine study only
Bar-pressing for cocaine, increasing number of presses each time (Progressive-ratio cocaine self-administration) cocaine study only
Bar-pressing for repeated good feeling (Brain stimulation reward threshold) cocaine study only
Blocking a learned response (Conditioned place preference expression) cocaine study only
Blocking the learning of a response (Conditioned place preference acquisition)
Measurement of ability to move (Locomotor tests)

All studies were sanctioned by BNL's Institutional Animal Care and Use Committee, and by corresponding committees at the collaborating institutions.

Last Modified: January 31, 2008