14: The action of heroin (morphine)
Heroin is an addictive drug, although not all users become addicted. Environment and the personality of the user are important in producing addiction. Heroin produces euphoria or pleasurable feelings and can be a positive reinforcer by interacting with the reward pathway in the brain. Indicate that you will explain how this happens.

15: Localization of opiate binding sites within the brain and spinal cord
When a person injects heroin (or morphine), the drug travels quickly to the brain through the bloodstream. Actually, heroin can reach the brain just as quickly if it is smoked (see description of image #25). Abusers also snort heroin to avoid problems with needles. In this case, the heroin doesn't reach the brain as quickly as if it were injected or smoked, but its effects can last longer. Once in the brain, the heroin is converted to morphine by enzymes; the morphine binds to opiate receptors in certain areas of the brain. Point to the areas where opiates bind (green dots). Part of the cerebral cortex, the VTA, nucleus accumbens, thalamus, brainstem, and spinal cord are highlighted. Show that the morphine binds to opiate receptors that are concentrated in areas within the reward pathway (including the VTA, nucleus accumbens, and cortex). Morphine also binds to areas involved in the pain pathway (including the thalamus, brainstem, and spinal cord). Binding of morphine to areas in the pain pathway leads to analgesia (loss of pain).

16: Morphine binding within the reward pathway
Reiterate that morphine binds to receptors on neurons in the VTA and in the nucleus accumbens. This is shown here within the reward pathway. Indicate that you will show how morphine activates this pathway on the next image.

17: Opiates binding to opiate receptors in the nucleus accumbens: increased dopamine release
This is a close-up view of a synapse in the nucleus accumbens. Three types of neurons participate in opiate action: one that releases dopamine (on the left), a neighboring terminal (on the right) that contains a different neurotransmitter (probably GABA for those who would like to know), and the post-synaptic cell that contains dopamine receptors (in pink). Show that opiates bind to opiate receptors (yellow) on the neighboring terminal and this sends a signal to the dopamine terminal to release more dopamine. [In case someone asks how, one theory is that opiate receptor activation decreases GABA release, which normally inhibits dopamine release, so dopamine release is increased.]

18: Rats self-administer heroin
Just as a rat will stimulate itself with a small electrical jolt (into the reward pathway), it will also press a bar to receive heroin. In this image, the rat is self-administering heroin through a small needle placed directly into the nuclues accumbens. The rat keeps pressing the bar to get more heroin because the drug makes the rat feel good. The heroin is positively reinforcing and serves as a reward. If the injection needle is placed in an area nearby the nucleus accumbens, the rat won't self-administer the heroin. Scientists have found that dopamine release is increased within the reward pathway of rats self-administering heroin. So, since more dopamine is present in the synaptic space, dopamine-dependent neurotransmission is augmented, causing the activation of the reward pathway.

19: Definition of tolerance
When drugs such as heroin are used repeatedly over time, tolerance may develop. Tolerance occurs when the person no longer responds to the drug in the way that person initially responded. Stated another way, it takes a higher dose of the drug to achieve the same level of response achieved initially. For example, in the case of heroin or morphine, tolerance develops rapidly to the analgesic effects of the drug. [The development of tolerance is not addiction, although many drugs that produce tolerance also have addictive potential.] Tolerance to drugs can be produced by several different mechanisms, but in the case of morphine or heroin, tolerance develops at the level of the cellular targets. For example, when morphine binds to opiate receptors, it triggers the inhibition of an enzyme (adenylate cyclase) that orchestrates several chemicals in the cell to maintain the firing of impulses. After repeated activation of the opiate receptor by morphine, the enzyme adapts so that the morphine can no longer cause changes in cell firing. Thus, the effect of a given dose of morphine or heroin is diminished.

20: Brain regions mediating the development of morphine tolerance
The development of tolerance to the analgesic effects of morphine involves different areas of the brain separate from those in the reward pathway. Point to the two areas involved here, the thalamus, and the spinal cord (green dots). Both of these areas are important in sending pain messages and are responsible for the analgesic effects of morphine. The parts of the reward pathway involved in heroin or morphine addiction are shown for comparison.

21: Definition of dependence
With repeated use of heroin, dependence also occurs. Dependence develops when the neurons adapt to the repeated drug exposure and only function normally in the presence of the drug. When the drug is withdrawn, several physiologic reactions occur. These can be mild (e.g., for caffeine) or even life threatening (e.g., for alcohol). This is known as the withdrawal syndrome. In the case of heroin, withdrawal can be very serious and the abuser will use the drug again to avoid the withdrawal syndrome.

22: Brain regions mediating the development of morphine dependence
The development of dependence to morphine also involves specific areas of the brain, separate from the reward pathway. In this case, point to the thalamus and the brainstem (green dots). The parts of the reward pathway involved in heroin or morphine addiction are shown for comparison. Many of the withdrawal symptoms from heroin or morphine are generated when the opiate receptors in the thalamus and brainstem are deprived of morphine.

23: Addiction vs dependence
As you have just explained, different parts of the brain are responsible for the addiction and dependence to heroin and opiates. Review the areas in the brain underlying the addiction to morphine (reward pathway) and those underlying the dependence to morphine (thalamus and brainstem). Thus, it is possible to be dependent on morphine, without being addicted to morphine. (Although, if one is addicted, they are most likely dependent as well.) This is especially true for people being treated chronically with morphine, for example, pain associated with terminal cancer. They may be dependent - if the drug is stopped, they suffer a withdrawal syndrome. But, they are not compulsive users of the morphine, and they are not addicted. Finally, people treated with morphine in the hospital for pain control after surgery are unlikely to become addicted; although they may feel some of the euphoria, the analgesic and sedating effects predominate. There is no compulsive use and the prescribed use is short-lived.