This program is brought to you by Emory University. [BLANK_AUDIO] The purposes of today's lecture are first, to connect the neurotransmitter, dopamine, with reward or feeling good processes and centers in brain. Second, to discuss the significance and importance of reward for survival. And third, to show that a re, release of dopamine occurs in response to cocaine and other drugs. You know that different brain regions have different functions. Feeling good or feeling rewarded are brain functions. Many such regions and circuits have been id, been identified, and it turns out that dopamine-containing neurons are in some of those regions. Before we talk about dopamine and reward, we can ask the most basic question of all. Why does reward exist? What purpose does feeling good have? Is its presence or evolution of meaningless, but pleasant, accident? Well, one can build a stronger argument that reward circuits in the brain are critical for the survival of our species. The idea is that reward circuits make us feel good when we do something for our survival. These include eating when hungry, drinking when thirsty, and engaging in sexual activities. We want to feel good, so we're motivated to do those things. Without reward circuits, one can claim that our survival would be threatened, or perhaps not possible. Further, you can argue that reward systems not only have to exist, but they have to be powerful because our survival is critical. Reward systems are not there for drugs. They're there for survival, according to these ideas. The implications that because drugs activate some of our very powerful reward systems, they very powerfully drive our behavior to repeatedly re-experience what feels good. It seems likely that drugs activate these centers by accident. At least some of these substances that activate can become addictive. These repeated efforts to re-experience what feels good leads to addiction in vulnerable people. The seeds of addiction are planted deep within our brain. We are, we are, by our nature, vulnerable to drugs. This image is the result of hundreds of experiments over many years. It's a schematic of the rat brain, showing some of the dopamine-containing neuronal circuits in the brain. The circles show specific brain regions, such as the nucleus accumbens, that receive dopamine-containing nerve terminals. Dopamine modulates the function connected with those regions. Another important part of this schematic is that it points out that the mesolimbic dopamine system is involved in reward. Not just drug reward, but other kinds of reward, including feeding, drinking and sexual activity. The linking of dopamine and reward is an important idea, and one of the foundations of current thinking in drug addiction research. Here again, is our dopamine and cocaine connection. Cocaine blocks the removal of dopamine from the synapse, thereby increasing the level of dopamine at the receptors, and increasing the stimulation of the receptors by dopamine. Behavioral studies, like drug self-administration, have shown that cocaine is rewarding. Its primary action is to inhibit the dopamine transporter. Thus, there is a clear dopamine-cocaine and dopamine-reward connection. Now, let's look at some of the experimental evidence for this. One of the kinds of experiments that we can perform routinely, is to measure the release of dopamine, and the levels of dopamine, in certain brain regions. To do this, a small probe is placed into a rat brain, for example, and this probe helps us measure dopamine levels in that area. The levels that it measures are the extracellular, or the synaptic levels of dopamine, which are the levels of dopamine that the receptors experience, not the dopamine inside the neurons. When cocaine, which is a rewarding stimulus, is given, dopamine levels dramatically increase. This diagram shows the relative levels of dopamine in a particular brain region, and the effect of cocaine on these levels. At early times before cocaine is given, the level of synaptic dopamine is relatively stable, shown at about 100. When cocaine is given, you can see that the level of cocaine dramatically increases, because the transporter is blocked. The removal of dopamine from extracellular spaces is block. But as cocaine levels fall, at around the ninth and tenth interval, the transporters regain their ability to function and dopamine levels begin to fall back to normal. But it's clear that cocaine causes an increase of extracellular dopamine and therefore, the cocaine-dopamine link is experimentally verified. Again, it is the extracellular levels that are connected to the receptors. So, cocaine causes a rise in dopamine levels, but what about other drugs? Well, it's been shown that cocaine is not the only drug that results in an increase in dopamine, in these very specific brain regions. Many experiments have shown that other drugs do it as well. They may not do it as directly as cocaine. Sometimes it may be more of an indirect action involving other neuronal circuits. But the classes of drugs that increase levels of dopamine include, the psychostimulants, which we've just seen because cocaine is a psychostimulant, opiates, ethanol, cannabinoids like THC, nicotine, caffeine and perhaps others. It's generally agreed that dopamine is an important regulator or modulator of drug reward. Because dopamine is involved in these very powerful reward systems that drugs affect, it is reasonable and important to study the effects of drugs on dopamine systems in brain. This is something that we will look at repeatedly in subsequent lectures.
