Drugs Affect Many Brain Pathways

A brain pathway (or neuronal pathway) is like a power line between two brain regions. A brain pathway is made up of interconnected neurons, and signals travel along them from one area of the brain to another.

Neurotransmitters are molecules that allow a signal to travel from one neuron to another. All drugs of abuse interfere with neurotransmitter signaling in some way. Neurons in different brain pathways use different neurotransmitters. Depending on which neurotransmitters they interfere with, drugs have varied effects in the brain.

Dopamine is the main neurotransmitter used by the reward pathway (also called the mesolimbic pathway, which is closely linked with the mesocortical pathway). But two other key pathways also use dopamine: the nigrostriatal pathway and the tuberoinfundibular pathway. Most drugs of abuse interfere with dopamine signaling, which affects all three of these pathways.

Nigrostriatal pathway: Substantia nigra to striatum

• Motor control
• Death of neurons in this pathway is linked to Parkinson's Disease

Mesolimbic and Mesocortical pathways: Ventral tegmental area to nucleus accumbens, amygdala, hippocampus, and prefrontal cortex

• Memory, motivation, emotion, reward, desire, and addiction
• Dysfunction is connected to hallucinations and schizophrenia

Tuberoinfundibular pathway: Hypothalamus to pituitary gland

• Hormone regulation, nurturing behavior, pregnancy, sensory processes

The neurotransmitters dopamine and serotonin (described below) are used by just a small number of neurons in the brain. Each of these neurons connects to thousands of others in many areas, giving them a great deal of influence over complex processes.

Many drugs of abuse interfere with serotonin signaling. These include cocaine, amphetamines, LSD, and alcohol. Serotonin-making neurons in the Raphe nuclei send signals to most areas of the brain, as well as the spinal cord.

Serotonin plays a role in many processes, including body temperature regulation, sleep, mood, appetite, and pain. Problems with serotonin signaling are linked to obsessive-compulsive disorder, anxiety disorders, and depression. Many medications for treating depression increase serotonin levels in the brain.

Glutamate and GABA (gamma-aminobutyric acid) are the brain's most plentiful neurotransmitters. Over half of all brain synapses use glutamate, and about one-third use GABA.

GABA is inhibitory and glutamate is excitatory, and the two work together to control many processes. Several drugs of abuse decrease or increase one or the other, changing the balance of glutamate and GABA. Sedative or depressant drugs tend to shift the balance toward GABA, decreasing brain activity. Stimulant drugs shift the balance toward glutamate, causing an energized, wakeful state in the user.

• Alcohol decreases glutamate activity.
• PCP, or "angel dust," increases glutamate activity.
• Caffeine increases glutamate activity and inhibits GABA release.
• Alcohol increases GABA activity.
• Tranquilizers increase GABA activity.