While we agree that dopamine is not the only important neurotransmitter in the brain, it's clear that looking at dopamine will tell us a great deal about drugs and reward. PET imaging can measure several components of the dopamine system in the brain, and one of these, for example, is the D2 dopamine receptor. PET can also measure energy metabolism, or glucose metabolism. The brain regions that are more active have greater metabolism. This image shows D2 dopamine receptors in the brains of both normal subjects and in those withdrawing from cocaine. The two different levels, or slices, of the brain from the same subject, are shown on the right, and the left. The levels of the receptors are reflected in the brightness of the regions. Brighter means more receptors. The bright, bilateral curved regions with the receptors within the brain are what's known as the basal ganglia. The top row of two slices or levels, show data for a normal subject, and the next two rows show data for cocaine users abstaining from drug for one and four months. The finding, which you can readily see, is that drug use is associated with lower D2 dopamine receptor levels, and that the return to normal is very slow, requiring months or longer. It's clear from what we know about neurotransmission, that changes in the level of receptors can have functional effects, and drug use changes dopamine neurotransmission. The slow return to normal indicates that the brain takes a long time to heal after drug use. For the first time, we have a hard biochemical measure of the rate of healing in the living human brain, which is made possible by imaging. While it is slow, there is healing. Staying away from drugs does promote healing, even though it takes a long time. These are very encouraging and hopeful data. We can examine the same time course of abstinence by looking at a different kind of PET scan, the PET scan of glucose utilization. The top left image shows a normal level of glucose utilization under these conditions. The top right shows glucose utilization after ten days of abstinence from cocaine. And the bottom shows en, energy metabolism after a 100 days of withdrawal. Again, using a different measure here, we see that it takes a long time for the brain to return to normal. As I said, I think that this has been an important discovery. What are the implications of a slow rate of healing? Well obviously, everyone involved with the drug user, including family, supporters, and treatment staff need to be aware of the long healing time. They can't expect miracles from short treatments. A successful treatment will have to continue in time, and because individuals vary, the duration of treatment may vary also. The drug user may have some relapses and require several treatment periods, but many people believe the brain eventually totally heals. The data show that it is gradually reversing towards normal. These findings and other considerations suggest that low levels of D2 dopamine reflect, receptors reflect a vulnerability to addiction in general. The image here shows D2 receptors for cocaine, which you've already seen, and those for methamphetamine and alcohol. Again, for all these drugs, and not just for cocaine, the levels of D2 dopamine receptors are reduced. What about other kinds of excessive activity that can have negative consequences and may be addicting? D2 receptor scans of obese subjects also show a reduction in D2 dopamine receptors. In gambling, D2 dopamine receptors correlate with the personality trait of impulsiveness, which is a broad measure of vulnerability to addiction. Lower levels of receptors suggest greater urgency for impulsiveness. Let me summarize. Dopamine systems in brain have been implicated in drug reward. PET scans reveal that the D2 dopamine receptor levels tend to be lower in drug users and in other kinds of vulnerable subjects. After abstinence, D2 levels return slowly towards normal. It may takes months to years, to become normal. This slow return has important implications for treatment and recovery. Do the low levels of reflec, of receptors reflect a deficiency in the reward system? Perhaps yes.
