11: Localization of cocaine "binding sites"
When a person smokes or snorts cocaine, it travels quickly to the brain. Although it reaches all areas of the brain, it concentrates in some specific areas. These are highlighted with the turquoise sprinkles; the VTA, the nucleus accumbens, and the caudate nucleus (lighter turquoise since the caudate is inside the hemisphere). Point out that cocaine concentrates especially in the reward areas that you have just discussed. Cocaine accumulation in other areas such as the caudate nucleus can explain other effects such as increased stereotypic behaviors (pacing, nail-biting, scratching, etc..)

12: Dopamine binding to receptors and uptake pumps in the nucleus accumbens
Explain that cocaine concentrates in areas of the brain that are rich in dopamine synapses. Review dopamine transmission in the nucleus accumbens. Point to dopamine in the synapse and to dopamine bound to dopamine receptors and to uptake pumps on the terminal.

13: Cocaine binding to uptake pumps: inhibition of dopamine uptake
Now, show what happens 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.

14: Increased cAMP produced in post-synaptic cell
In a closer view, show how this affects the function of the cell. 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.

15: Summary: cocaine binding in nucleus accumbens and activation of reward pathway
Show the "big picture," As a result of cocaine's actions in the nucleus accumbens (point to the sprinkles of cocaine in the nuc. acc.), there are increased impulses leaving the nucleus accumbens to activate the reward system. Indicate that 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).

16: Positron emission tomography (PET) scan of a person on cocaine
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. 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.

17: Localization of opiate binding sites
When a person injects heroin or morphine, it too travels quickly to the brain. Point to the areas where opiates concentrate. The VTA, nucleus accumbens, caudate nucleus and thalamus are highlighted. The opiates bind to opiate receptors that are concentrated in areas within the reward system. Indicate that the action of opiates in the thalamus contributes to their ability to produce analgesia.

18: Opiates binding to opiate receptors in the nucleus accumbens: increased dopamine release
Show how opiates activiate the reward system using the nucleus accumbens as an example. Explain that the action is a little more complicated than cocaine's because more than two neurons are involved. Point out that three neurons participate in opiate action: the dopamine terminal, another terminal (on the right) containing a different neurotransmitter (probably GABA for those that would like to know), and the post-synaptic cell containing dopamine receptors. Show that opiates bind to opiate receptors (green) on the neighboring terminal and this sends a signal to the dopamine terminal to release more dopamine. [In case an inquisitive student asks how, one theory is that opiate receptor activation decreases GABA release, which normally inhibits dopamine release, so dopamine release is increased.]