Page 53 - Pagetit

NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

result in the propagation of a signal through the generation of second
messengers. The second messenger can either open an ion channel, or can
initiate a series of biochemical reactions leading to longer-term changes in
neuronal function in the postsynaptic cell. There are many different second
messenger pathways; this increases the diversity of signals that can be sent,
and the consequences of those signals. An example of this type of receptor is
called a G protein-coupled receptor. Dopamine receptors are G protein-
coupled receptors, and depending upon the subtype of dopamine receptor,
ligand binding can either stimulate or inhibit the production of cyclic
adenosine monophosphate (cAMP). Psychoactive substances can have long-
term effects on cAMP function, as will be discussed in more detail at the end
of this chapter.
Receptors play a role not only in the immediate, reinforcing effects of
psychoactive substances, but also in the processes of tolerance and
withdrawal. Specific examples will be discussed in Chapter 4, but as one
example, tolerance to benzodiazepines and barbiturates develops through
changes in GABA-A receptor structure. The receptor adapts to the presence
of the substance, leading to tolerance. Thus, higher doses are required to have
an effect. When the substance is removed, withdrawal symptoms appear,
because of these structural changes which have occurred to accommodate
the presence of the substance.

Neurotransmitters
A neurotransmitter can be defined as a chemical substance that is released
synaptically from one neuron and that affects another cell in a specific
manner (Kandel & Schwartz, 1985). A neurotransmitter must also meet the
following criteria:
— synthesized in the neuron;

—present in the presynaptic neuron;
—released in sufficient quantity to have a postsynaptic effect;
— has the same effect whether released by natural means (endogenously)
or whether applied as a drug (exogenously).
It must also have a specific mechanism for its removal from the synaptic cleft.
Many types of neurotransmitters have been discovered so far, but in general
there are three categories: amino acid neurotransmitters, amino acid-derived
neurotransmitters, and peptides, which are chains of amino acids. The amino
acid transmitters include glutamate, GABA, glycine and aspartate. The
monoamines (norepinephrine and dopamine (catecholamines) and
serotonin (indoleamine) are derived from amino acids. Large molecule
peptide neurotransmitters are generally synthesized in the cell body, and
transported along the axons to the terminal buttons. Small molecule
neurotransmitters can be synthesized in the terminals.

32

Chapter_2 32 19.1.2004, 11:28