As we discussed, a drug must get into the brain in order to have an effect. During this lecture, we address what the drugs have to do in the brain to generate a feeling that is positive and something that you want to feel again and again. To understand this, we need to discuss synaptic transmission. Synaptic transmission is a process that occurs in the brain, and that is fundamental to how the brain works. Understanding it is required for understanding how the brain functions. It's also a key for understanding how drugs produce their effect. So, this is going to be very important and fun. There are different words used. And I just used the phrase synaptic transmission. This is the same as neurotransmission. And you will see either term or some hybrid of these words throughout this course. Here we see a picture of the brain, and like any organ in the body, the brain has cells specialized for it's function. If you take a slice of the brain, and look at it under a microscope, you will see a certain cell type that we call nerve cells or neurons. And others as well. Neurons are uniquely shaped cells tailor made for an organ like the brain. The nerve cells has a cell body, as of course do all cells. But it has many processes that extend out from the cell body. There are many that are called dendrites. And dendrites collect signals that come from other cells. The cell body also has an axonal extension or an axon that reaches out to other nerve cells. At the end of the axon is a nerve terminal. And the nerve terminals make very close contact, not an actual physical contact, but a very close apposition with the next cell, or a dendrite on the next cell. So, we have neuronal cell bodies, dendrites, axons, and the nerve terminals. Note that axons can be very long, so by means of an axon, a given nerve cell can influence another nerve cell or actually many nerve cells that are quite a distance away. This diagram shows that neurons form chains or circuits in the brain. Let's look closely at how this works. Here we see a nerve cell body, the axon, and the nerve terminal. The nerve terminal releases substances called neurotransmitters, and these neurotransmitters bind to receptors on the next nerve cell in the circuit. Normally, the way this works is that a nerve impulse or an action potential, starts in a cell body. And this travels down the axon and invades the nerve terminal. When the action potential, or the impulse, invades the nerve terminal, these chemical substances, or chemical signals, that we call neurotransmitters are released. They then diffuse across the space we call the synaptic cleft, or the synaptic gap right here, which is that space between the cells. And the neurotransmitters bind the receptors on the next cell. Once they bind to the receptors on the next cell in the circuit. That cell can then be activated by this binding because the chemical substances, when bound to the receptors, can produce an activation of the next cell. This activation can result in another action potential or impulse, which travels down the axon to the next or to its nerve terminal which causes a release of chemical substances on to the next cell and so forth. This process can go on along the chain containing many nerve cells. This is how circuits or pathways maintain communication. The circuit uses alternating electrical impulses and chemical signaling to maintain activity. And to produce some function. So I stress that it's an alternating electrical and chemical signaling that occurs in the brain allowing a circuit of neurons to ultimately produce some physiological effect. When it comes to understanding drugs and how drugs work the synapse is the most important part. It's important for understanding how antidepressants work, how antipsychotic drugs work, and so forth. So, the synapse is the template upon which we build our knowledge of many, and maybe most drugs, in the brain. Now let me show you an actual picture of nerve terminal obtained with an electron microscope. The nerve terminal is here in the center, and the membrane of the nerve terminal is generally right around these vesicles. You can see the space right here, which is the synaptic gap, you can see the vesicles, you can see them lining up along the membrane just as though they were about to release their contents and you can see, in this case, a post-synaptic thickening. A thickening in the next nerve cell, or the next dendrite, which is important for synaptic transmission. Now, let's consider a neurotransmitter, called dopamine. The slide shows a nerve terminal containing storage vesicles. There are receptors on the post-synaptic cell. And you can see the synaptic gap. When a nerve impulse or action potential invades this nerve terminal, the vesicles fuse with the membrane and secrete the chemical neurotransmitters into the space, into the synaptic space, where they diffuse and interact with the receptors. By interacting with the receptors, signals are set up in this post-synaptic cell. Now, while a neurotransmitter has to act at the receptors to produce a signal, its signaling action has to be eventually stopped. In other words, the neurotransmitter has to be removed from the region of the receptors so that the signaling is discreet. If the signaling didn't stop, but went on and on, it would be a burst of continuous noise rather than a discrete signal. So, neurotransmission is an on off process and it's very brief, of the order of milliseconds or thousandths of a second. It occurs quickly. In the case of dopamine, the way the dopamine molecules are removed from the synaptic space is by transport. Dopamine is taken back up into the nerve terminal. When the neurotransmitter's taken up and put back into the nerve terminal, it's removed from the synaptic gap. This re-uptake or removal of dopamine from the region of the receptors is how neurotransmission, in this case, is terminated. So, in general, neurotransmitters are made in the nerve cells. They're stored in vesicles. They're released by action potentials or electrical impulses. They interact with receptors. And finally, they must be removed from receptors. To summarize, there are three major events that we'll be talking about in neurotransmission. The release of neurotransmitter. Receptor interaction, and the removal from receptors. There are many neurotransmitters, and many addictive drugs focus on, and work at least partly through different neurotransmitters. For example, psycho stimulants like cocaine work directly through dopamine. A stimulant like nicotine will first bind at acetylcholine receptors, but then later they involve dopamine. We'll look at all of these in more detail later on, but there are many neurotransmitters found in the brain that are involved in signaling. And we have to know about them, at least in general, if we're going to understand how drugs work.
