The Brain on Drugs
The brain consists of several large regions, each responsible for some of the activities vital for living. These include the brainstem, cerebellum, limbic system, diencephalon, and cerebral cortex (Figure 1).
The brainstem is the part of the brain that connects the brain and the spinal cord. It controls many basic functions, such as heart rate, breathing, eating, and sleeping. The brainstem accomplishes this by directing the spinal cord, other parts of the brain, and the body to do what is necessary to maintain these basic functions.
The cerebellum, which represents only one-eighth of the total weight of the brain, coordinates the brain's instructions for skilled repetitive movements and for maintaining balance and posture. It is a prominent structure located above the brainstem.
Figure 1: This drawing of a brain cut in half demonstrates
some of the major regions of the brain.
On top of the brainstem and buried under the cortex, there is a set of more evolutionarily primitive brain structures called the limbic system (Figure 2). The limbic system structures are involved in many of our emotions and motivations, particularly those that are related to survival, such as fear, anger, and emotions related to sexual behavior. The limbic system is also involved in feelings of pleasure that are related to our survival, such as those experienced from eating and sex. Two large limbic system structures called the amygdala and hippocampus are also involved in memory. One of the reasons that drugs of abuse can exert such powerful control over our behavior is that they act directly on the more evolutionarily primitive brainstem and limbic structures, which can override the cortex in controlling our behavior. In effect, they eliminate the most human part of our brain from its role in controlling our behavior.
The diencephalon, which is also located beneath the cerebral hemispheres, contains the thalamus and hypothalamus (Figure 2). The thalamus is involved in sensory perception and regulation of motor functions (i.e., movement). It connects areas of the cerebral cortex that are involved in sensory perception and movement with other parts of the brain and spinal cord that also have a role in sensation and movement. The hypothalamus is a very small but important component of the diencephalon. It plays a major role in regulating hormones, the pituitary gland, body temperature, the adrenal glands, and many other vital activities.
Figure 2: This drawing of a brain cut in half demonstrates
some of the brain's internal structures. The amygdala
and hippocampus are actually located deep within the
brain, but are shown as an overlay in the
approximate areas that they are located.
The cerebral cortex, which is divided into right and left hemispheres, encompasses about two-thirds of the brain mass and lies over and around most of the remaining structures of the brain. It is the most highly developed part of the human brain and is related to thinking, perceiving, and producing and understanding language. It is also the most recent structure in the history of brain evolution. The cerebral cortex can be divided into areas that each have a specific function (Figure 3). For example, there are specific areas involved in vision, hearing, touch, movement, and smell. Other areas are critical for thinking and reasoning. Although many functions, such as touch, are found in both the right and left cerebral hemispheres, some functions are found in only one cerebral hemisphere. For example, in most people, language abilities are found in the left hemisphere.
Figure 3: This drawing of a brain cut in half demonstrates the lobes of the cerebral
cortex and their functions.
Nerve Cells and Neurotransmission
The brain is made up of billions of nerve cells. Typically, a neuron contains three important parts (Figure 4): a central cell body that directs all activities of the neuron; dendrites, short fibers that receive messages from other neurons and relay them to the cell body; and an axon, a long single fiber that transmits messages from the cell body to the dendrites of other neurons or to body tissues, such as muscles. Although most neurons contain all of the three parts, there is a wide range of diversity in the shapes and sizes of neurons as well as their axons and dendrites.
The transfer of a message from the axon of one nerve cell to the dendrites of another is known as neurotransmission. Although axons and dendrites are located extremely close to each other, the transmission of a message from an axon to a dendrite does not occur through direct contact. Instead, communication between nerve cells occurs mainly through the release of chemical substances into the space between the axon and dendrites (Figure 5). This space is known as the synapse. When neurons communicate, a message, traveling as an electrical impulse, moves down an axon and toward the synapse. There it triggers the release of molecules called neurotransmitters from the axon into the synapse. The neurotransmitters then diffuse across the synapse and bind to special molecules, called receptors, that are located within the cell membranes of the dendrites of the adjacent nerve cell. This, in turn, stimulates or inhibits an electrical response in the receiving neuron's dendrites. Thus, the neurotransmitters act as chemical messengers, carrying information from one neuron to another.
There are many different types of neurotransmitters, each of which has a precise role to play in the functioning of the brain. Generally, each neurotransmitter can only bind to a very specific matching receptor. Therefore, when a neurotransmitter couples to a receptor, it is like fitting a key into a lock. This coupling then starts a whole cascade of events at both the surface of the dendrite of the receiving nerve cell and inside the cell. In this manner, the message carried by the neurotransmitter is received and processed by the receiving nerve cell. Once this has occurred, the neurotransmitter is inactivated in one of two ways. It is either broken down by an enzyme or reabsorbed back into the nerve cell that released it. The reabsorption (also known as re-uptake) is accomplished by what are known as transporter molecules (Figure 5). Transporter molecules reside in the cell membranes of the axons that release the neurotransmitters. They pick up specific neurotransmitters from the synapse and carry them back across the cell membrane and into the axon. The neurotransmitters are then available for reuse at a later time.
As noted above, messages that are received by dendrites are relayed to the cell body and then to the axon. The axons then transmit the messages, which are in the form of electrical impulses, to other neurons or body tissues. The axons of many neurons are covered in a fatty substance known as myelin. Myelin has several functions. One of its most important is to increase the rate at which nerve impulses travel along the axon. The rate of conduction of a nerve impulse along a heavily myelinated axon can be as fast as 120 meters/second. In contrast, a nerve impulse can travel no faster than about 2 meters/second along an axon without myelin. The thickness of the myelin covering on an axon is closely linked to the function of that axon. For example, axons that travel a long distance, such as those that extend from the spinal cord to the foot, generally contain a thick myelin covering to facilitate faster transMission of the nerve impulse. (Note: The axons that transmit messages from the brain or spinal cord to muscles and other body tissues are what make up the nerves of the human body. Most of these axons contain a thick covering of myelin, which accounts for the whitish appearance of nerves.)'
Effects of Drugs of Abuse on the Brain
Pleasure, which scientists call reward, is a very powerful biological force for our survival. If you do something pleasurable, the brain is wired in such a way that you tend to do it again. Life-sustaining activities, such as eating, activate a circuit of specialized nerve cells devoted to producing and regulating pleasure. One important set of these nerve cells, which uses a chemical neurotransmitter called dopamine, sits at the very top of the brainstem in the ventral tegmental area (VTA) (Figure 6). These dopamine-containing neurons relay messages about pleasure through their nerve fibers to nerve cells in a limbic system structure called the nucleus accumbens. Still other fibers reach to a related part of the frontal region of the cerebral cortex. So, the pleasure circuit, which is known as the mesolimbic dopamine system, spans the survival-oriented brainstem, the emotional limbic system, and the frontal cerebral cortex.
All drugs that are addicting can activate the brain's pleasure circuit. Drug addiction is a biological, pathological process that alters the way in which the pleasure center, as well as other parts of the brain, functions. To understand this process, it is necessary to examine the effects of drugs on neurotransmission. Almost all drugs that change the way the brain works do so by affecting chemical neurotransmission. Some drugs, like heroin and LSD, mimic the effects of a natural neurotransmitter. Others, like PCP, block receptors and thereby prevent neuronal messages from getting through. Still others, like cocaine, interfere with the molecules that are responsible for transporting neurotransmitters back into the neurons that released them (Figure 7). Finally, some drugs, such as methamphetamine, act by causing neurotransmitters to be released in greater amounts than normal.
Figure 7: When cocaine enters the brain, it blocks the dopamine transporter from
pumping dopamine back into the transmitting neuron, flooding the synapse with
dopamine. This intensifies and prolongs the stimulation of receiving neurons in the
brain's pleasure circuits, causing a cocaine "high."
Prolonged drug use changes the brain in fundamental and long-lasting ways. These long-lasting changes are a major component of the addiction itself. It is as though there is a figurative "switch" in the brain that "flips" at some point during an individual's drug use. The point at which this "flip" occurs varies from individual to individual, but the effect of this change is the transformation of a drug abuser to a drug addict.