Mechanism of Action
 

Opiates elicit their powerful effects by activating opiate receptors that are widely distributed throughout
the brain and body. Once an opiate reaches the brain, it quickly activates the opiate receptors that are
found in many brain regions and produces an effect that correlates with the area of the brain involved.
Two important effects produced by opiates, such as morphine, are pleasure (or reward) and pain relief.
The brain itself also produces substances known as endorphins that activate the opiate receptors.
Research indicates that endorphins are involved in many things, including respiration, nausea, vomiting,
pain modulation, and hormonal regulation.

 When opiates are prescribed by a physician for
 the treatment of pain and are taken in the
 prescribed dosage, they are safe and there is
 little chance of addiction. However, when
 opiates are abused and taken in excessive doses,
 addiction can result. Findings from animal
 research indicate that, like cocaine and other
 abused drugs, opiates can also activate the
 brain's reward system. When a person injects,
 sniffs, or orally ingests heroin (or morphine), the
 drug travels quickly to the brain through the
 bloodstream. Once in the brain, the heroin is
 rapidly converted to morphine, which then activates opiate receptors located throughout the brain,
 including within the reward system. (Note: Because of its chemical structure, heroin penetrates the
 brain more quickly than other opiates, which is probably why many addicts prefer heroin.) Within the
 reward system, the morphine activates opiate receptors in the VTA, nucleus accumbens, and cerebral
 cortex (refer to the Introduction for information on the reward system). Research suggests that
 stimulation of opiate receptors by morphine results in feelings of reward and activates the pleasure
 circuit by causing greater amounts of dopamine to be released within the nucleus accumbens. This
 causes an intense euphoria, or rush, that lasts only briefly and is followed by a few hours of a relaxed,
 contented state. This excessive release of dopamine and stimulation of the reward system can lead to
 addiction.

 Opiates also act directly on the respiratory center in the brainstem, where they cause a slowdown in
 activity. This results in a decrease in breathing rate. Excessive amounts of an opiate, like heroin, can
 cause the respiratory centers to shut down breathing altogether. When someone overdoses on heroin,
 it is the action of heroin in the brainstem respiratory centers that can cause the person to stop
 breathing and die.

 As mentioned earlier, the brain itself produces endorphins that have an important role in the relief or
 modulation of pain. Sometimes, though, particularly when pain is severe, the brain does not produce
 enough endorphins to provide pain relief. Fortunately, opiates, such as morphine are very powerful
 pain relieving medications. When used properly under the care of a physician, opiates can relieve
 severe pain without causing addiction.Feelings of pain are produced when specialized
                                         nerves are activated by trauma to some part of
                                         the body, either through injury or illness. These
                                         specialized nerves, which are located
                                         throughout the body, carry the pain message to
                                         the spinal cord. After reaching the spinal cord,
                                         the message is relayed to other neurons, some
                                         of which carry it to the brain. Opiates help to
                                         relieve pain by acting in both the spinal cord
                                         and brain. At the level of the spinal cord,
                                         opiates interfere with the transmission of the
                                         pain messages between neurons and therefore
                                         prevent them from reaching the brain. This
                                         blockade of pain messages protects a person
                                         from experiencing too much pain. This is
                                         known as analgesia.

 Opiates also act in the brain to help relieve pain, but the way in which they accomplish this is different
 than in the spinal cord.

 There are several areas in the brain that are involved in interpreting pain messages and in subjective
 responses to pain. These brain regions are what allow a person to know he or she is experiencing pain
 and that it is unpleasant. Opiates also act in these brain regions, but they don't block the pain
 messages themselves. Rather, they change the subjective experience of the pain. This is why a
 person receiving morphine for pain may say that they still feel the pain but that it doesn't bother them
 anymore.

 Although endorphins are not always adequate to relieve pain, they are very important for survival. If
 an animal or person is injured and needs to escape a harmful situation, it would be difficult to do so
 while experiencing severe pain. However, endorphins that are released immediately following an
 injury can provide enough pain relief to allow escape from a harmful situation. Later, when it is safe,
 the endorphin levels decrease and intense pain may be felt. This also is important for survival. If the
 endorphins continued to blunt the pain, it would be easy to ignore an injury and then not seek medical
 care.

 There are several types of opiate receptors, including the delta, mu, and kappa receptors. Each of
 these three receptors is involved in controlling different brain functions. For example, opiates and
 endorphins are able to block pain signals by binding to the mu receptor site. The powerful new
 technology of cloning has enabled scientists to copy the genes that make each of these receptors.
 This in turn is allowing researchers to conduct laboratory studies to better understand how opiates act
 in the brain and, more specifically, how opiates interact with each opiate receptor to produce their
 effects. This information may eventually lead to more effective treatments for pain and opiate
 addiction.

 The following activities, when used along with the magazine on opiates, will help explain to students
 how these substances change the brain and the body.