Rats will press a bar to get an injection of cocaine or heroin (self-administration). The rat keeps pressing to get more cocaine or heroin because the drugs make the rat feel so good. This is called positive reinforcement, or reward. Natural rewards include food, water and sex - each is required to maintain survival of our species.
Animals and people will continue to exhibit a behavior that is rewarding - and they will cease that behavior when the reward is no longer present. There is actually a part of the brain that is activated by natural rewards and by artificial rewards such as addictive drugs. This part of the brain is called the reward system.
Neuroscientists have been able to pinpoint the exact parts of the brain involved, with the help of the rats. Rats will also self-administer addictive drugs directly into their brains, but only into a specific area of the reward system.
If the injection needle is moved less than a millimeter away from this crucial area, the rat won't press the lever for more drug. So based on information from working with the rats, scientists have drawn a map of the brain, and located the structures and pathways that are activated when an addictive drug is taken voluntarily.
This is a view of the brain cut down the middle. An important part of the reward system is shown and the major structures are highlighted: the ventral tegmental area (VTA), the nucleus accumbens (nuc. acc.) and the prefrontal cortex. Also, the pathway connecting these structures is highlighted.
The information travels from the VTA to the nucleus accumbens and then up to the prefrontal cortex. This pathway is activated by a rewarding stimulus. (Note to scientists - this is not the only pathway activated by reward, other structures are involved too, but only this part of the pathway is shown for simplicity.)
A Picture Of The Reward Pathway
Scientists located the structures important for the addictive nature of drugs. A rat will self-administer cocaine directly into the nucleus accumbens (or the VTA) to activate the pathway. If the injection is placed in another area, the rat will not press the lever to receive the drug. Scientists know a lot more than where the drug acts to produce rewarding effects - they also know how the drugs work.
Cocaine concentrates in areas of the brain that are rich in dopamine synapses.
When cocaine is present in the synapse. Cocaine (turquoise) binds to the uptake pumps and prevents them from removing dopamine from the synapse. This results in more dopamine in the synapse, and more dopamine receptors are activated.
A Picture Of Cocaine Binding To Uptake Pumps
The increased activation of dopamine receptors causes increased production of cAMP inside the post-synaptic cell. This causes many changes inside the cell that lead to abnormal firing patterns.
With continued use of cocaine, the body relies on this drug to maintain rewarding feelings. The person is no longer able to feel the positive reinforcement or pleasurable feelings of natural rewards (food, water, sex).
Cocaine has other actions in the brain in addition to activating reward. Scientists have the ability to see how cocaine actually affects brain function in people. The PET scan allows one to see how the brain uses glucose; glucose provides energy to each neuron so it can perform work. The scans show where the cocaine interferes with the brain's use of glucose - or its metabolic activity.
A PET Scan Of A Person On Cocaine
The left scan is taken from a normal, awake person. The red color shows the highest level of glucose utilization (yellow represents less utilization and blue shows the least).
The right scan is taken from a cocaine abuser on cocaine. It shows that the brain cannot use glucose nearly as effectively - show the loss of red compared to the left scan.
There are many areas of the brain that have reduced metabolic activity. The continued reduction in the neurons' ability to use glucose (energy) results in disruption of many brain functions.