Below is a narrated animation of drug addiction mechanism. Click here to license this video on Alila Medical Media website.

The Brain Reward Pathway

Addiction is a neurological disorder that affects the reward system in the brain. In a healthy person, the reward system reinforces important behaviors that are essential for survival such as eating, drinking, sex, and social interaction. For example, the reward system ensures that you reach for food when you are hungry, because you know that after eating you will feel good. In other words, it makes the activity of eating pleasurable and memorable, so you would want to do it again and again whenever you feel hungry. Drugs of abuse hijack this system, turning the person’s natural needs into drug needs.
The brain consists of billions of neurons, or nerve cells, which communicate via chemical messages, or neurotransmitters. When a neuron is sufficiently stimulated, an electrical impulse called an action potential is generated and travels down the axon to the nerve terminal. Here, it triggers the release of a neurotransmitter into the synaptic cleft – a space between neurons. The neurotransmitter then binds to a receptor on a neighboring neuron, generating a signal in it, thereby transmitting the information to that neuron.

Fig. 1: Structure of a neuron, with details of myelin and synapse. Click on image to see it on Alila Medical Media website where the image is also available for licensing.

 
The major reward pathways involve transmission of the neurotransmitter dopamine from the ventral tegmental area – the VTA – of the midbrain to the limbic system and the frontal cortex. Engaging in enjoyable activities generates action potentials in dopamine-producing neurons of the VTA. This causes dopamine release from the neurons into the synaptic space. Dopamine then binds to and stimulates dopamine-receptor on the receiving neuron. This stimulation by dopamine is believed to produce the pleasurable feelings or rewarding effect. Dopamine molecules are then removed from the synaptic space and transported back in to the transmitting neuron by a special protein called dopamine-transporter.

Fig. 2: The dopaminergic pathways. Click on image to see it on Alila Medical Media website where the image is also available for licensing.

Mechanism of Drug Addiction in the Brain

Most drugs of abuse increase the level of dopamine in the reward pathway. Some drugs such as alcohol, heroin, and nicotine indirectly excite the dopamine-producing neurons in the VTA so that they generate more action potentials. Cocaine acts at the nerve terminal. It binds to dopamine-transporter and blocks the re-uptake of dopamine. Methamphetamine – a psychostimulant – acts similarly to cocaine in blocking dopamine removal. In addition, it can enter the neuron, into the dopamine-containing vesicles where it triggers dopamine release even in the absence of action potentials.

Fig. 3: Methamphetamine action on dopamine synapse. Click on image to see it on Alila Medical Media website where the image is also available for licensing.

Different drugs act different way but the common outcome is that dopamine builds-up in the synapse to a much greater amount than normal. This causes a continuous stimulation, maybe over-stimulation of receiving neurons and is responsible for prolonged and intense euphoria experienced by drug users. Repeated exposure to dopamine surges caused by drugs eventually de-sensitizes the reward system. The system is no longer responsive to everyday stimuli; the only thing that is rewarding is the drug. That is how drugs change the person’s life priority. After some time, even the drug loses its ability to reward and higher doses are required to achieve the rewarding effect. This ultimately leads to drug overdose.

Below is a narrated animation of brain anatomy. Click here to license this video on Alila Medical Media website.

The human brain is divided into three major parts :
– The cerebrum  – the largest part of human brain. The cerebrum enables sensory perception and controls voluntary motor actions.
– The cerebellum  – the cerebellum lies inferior to the cerebrum at the back of the head. It is mostly involved in coordination of movement and fine tuning of motor activities.
– The brainstem – the brainstem is located at the base of the brain and is continuous to the spinal cord. The major components of the brainstem, from rostral to caudal, are : midbrain, pons and medulla oblongata. The brainstem houses all nerve connections between different parts of the central nervous system. It provides innervation to the head and neck via cranial nerves. It also contains nuclei associated with important body functions such as regulation of blood pressure, respiration, swallowing, bladder control, sleep cycle, … among others.

Fig. 1: Median section of human brain. Click on image to see it on Alila Medical Media website where the image is also available for licensing.

On top of the brainstem, and sometimes classified as part of it, is the diencephalon. The main components of the diencephalon are:
– The thalamus – the thalamus serves as a gateway relaying sensory signals originated throughout the body to the cerebral cortex. It is also involved in emotional and memory functions.
– The hypothalamus – the hypothalamus is the major control center of the autonomic nervous system and plays essential role in homeostatic regulation. The hypothalamus links the nervous system to the endocrine system via the pituitary gland. It also contains nuclei involved in regulation of body temperature, food and water intake, sleep and wake cycle, memory and emotional behavior.
The cerebrum consists of two cerebral hemispheres. The left hemisphere controls the right half of the body. The right hemisphere controls the left half of the body. The two hemispheres are separated by a deep groove called the longitudinal fissure. Each hemisphere has a number of folds called gyri separated by grooves called sulci. A major landmark is the central sulcus.
The cerebrum has four major lobes. The frontal lobe is situated anterior to the central sulcus. It is associated mainly with voluntary motor functions, planning, motivation, emotion and social judgment.
Posterior to the central sulcus is the parietal lobe. This lobe is mainly concerned with sensory functions of the somatosensory category such as touch, stretch, movement, temperature and pain.
The temporal lobe is separated from the frontal and parietal lobes by the lateral sulcus. The temporal lobe is associated with hearing, learning, visual memory and language.
The occipital lobe is located at the rear of the cerebrum. This is the visual processing center of the brain.

Fig. 2: Lobes of the brain. Click on image to see it on Alila Medical Media website where the image is also available for licensing.

At first glance, the two hemispheres look identical, but research has found a number of differences between them. This is called lateralization of brain function. For example, the language formation areas – the Wernicke’s and Broca’s areas – are usually located in the left hemisphere of right-handed people. Lesions to these areas result in language comprehension deficits or speech disorders. The corresponding areas in the right hemisphere are responsible for emotional aspect of language. Lesions to these areas do not affect speech comprehension and formation, but result in emotionless speech and inability to understand the emotion behind the speech such as sarcasm or a joke.