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2. BRAIN MECHANISMS: NEUROBIOLOGY AND NEUROANATOMY

There are distinct regions of the brain where cell bodies for a specific
neurotransmitter exist, and other regions or “projection areas” where the
axons from those cell bodies project to, and where the neurotransmitter is
ultimately released. Thus, not every neurotransmitter is released in every area
of the brain. This allows certain areas of the brain to perform specific
functions. Some of the more important neurotransmitters with respect to
the neuroscience of dependence are discussed below.

Acetylcholine

Acetylcholine is a neurotransmitter formed from choline, which is derived
from the diet. It is formed by an enzymatic reaction with coenzyme A.
Acetylcholine plays an important role in learning and memory, and is thought
to be involved in Alzheimer disease. Neurons that synthesize and release
acetylcholine are called cholinergic neurons. The cell bodies are located in
the basal nucleus, but they project widely throughout the cortex.
Acetylcholine receptors are ligand-gated cation channels, and there are two
main subtypes, nicotinic and muscarinic, named on account of their
responsiveness to nicotine and muscarine respectively. Receptors for
acetylcholine have been implicated in nicotine dependence and may also
contribute to the effects of cocaine and amphetamine.

γ-aminobutyric acid
GABA is widely distributed throughout the nervous system, and is an amino
acid formed from the amino acid glutamate. GABA is an inhibitory
neurotransmitter that acts through two distinct receptor subtypes, named
GABA-A and GABA-B. The GABA-A receptors form a chloride ion channel.
The binding of GABA to GABA-A receptors opens this channel resulting in
the rapid diffusion of chloride ions into the cell, thus hyperpolarizing the
cell and making it less likely to fire an action potential. The sedative, anxiety-
reducing effects of benzodiazepines, barbiturates and alcohol are derived
from their effects on the GABA-A receptor. Anti-epileptic medications also
act to facilitate the function of the GABA-A receptor, and blocking the effects
of GABA can lead to seizures. This is why withdrawal from benzodiazepines
or alcohol can be associated with seizures. The GABA-B receptors are G
protein-coupled receptors, and binding of GABA to the GABA-B receptor

opens a potassiumchannel.

Glutamate
Glutamate is an excitatory amino acid neurotransmitter found throughout
the brain. It is derived from proteins in the diet and is produced by the
metabolic processes of the cells. Glutamate acts at four receptor subtypes;
NMDA, AMPA, kainate, and metabotropic glutamate receptors. Some of

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