377
CHAPTER TEN
Nervous System I
D
rug abuse and addiction are long-stand-
ing problems. A 3,500-year-old Egyptian
document decries reliance on opium. In
the 1600s, a smokable form of opium enslaved
many Chinese, and the Japanese and Europeans
discovered the addictive nature of nicotine.
During the American Civil War, morphine was a
widely used painkiller; cocaine was introduced
a short time later to relieve veterans addicted to
morphine. Today, abuse of drugs intended for
medical use continues. LSD was originally used
in psychotherapy but was abused in the 1960s
as a hallucinogen. PCP was an anesthetic before
being abused in the 1980s.
Why do certain drugs compel a person to
repeatedly use them, even when knowing that
doing so is dangerous? Eating hot fudge sun-
daes is highly enjoyable, but we usually don’t feel
driven to consume them repeatedly. The biol-
ogy of neurotransmission helps to explain drug
addiction.
When a drug alters the activity of a neuro-
transmitter on a postsynaptic neuron, it either
halts or enhances synaptic transmission. A drug
that binds to a receptor, blocking a neurotransmit-
ter from binding, is called an
antagonist.
A drug
that activates the receptor, triggering an action
potential, or that helps a neurotransmitter to bind,
is called an
agonist.
The eF
ect of a drug depends
upon whether it is an antagonist or an agonist; on
the particular behaviors the aF
ected neurotrans-
mitter normally regulates; and in which parts of
the brain drugs affect neurotransmitters and
their binding to receptors. Many addictive sub-
stances bind to receptors for the neurotransmit-
ter dopamine, in a brain region called the nucleus
accumbens.
With repeated use of an addictive substance,
the number of receptors it targets can decline.
When this happens, the person must use more
of the drug to feel the same eF
ect. ±or example,
neural pathways that use the neurotransmitter
norepinephrine control arousal, dreaming, and
mood. Amphetamine enhances norepinephrine
activity, thereby heightening alertness and mood.
Amphetamine’s structure is so similar to that of
norepinephrine that it binds to norepinephrine
receptors and triggers the same changes in the
postsynaptic membrane.
Cocaine has a complex mechanism of action,
both blocking reuptake of norepinephrine and
binding to molecules that transport dopamine to
postsynaptic cells. The drug valium causes relax-
ation and inhibits seizures and anxiety by helping
GABA, an inhibitory neurotransmitter used in a
third of the brain’s synapses, bind to receptors on
postsynaptic neurons. Valium is therefore a GABA
agonist.
Nicotine causes addiction, which supplies
enough of the other chemicals in cigarette smoke
to destroy health. An activated form of nicotine
binds postsynaptic nicotinic receptors that nor-
mally receive acetylcholine. When su²
cient nico-
tine binds, a receptor channel opens, allowing
positive ions in (³
g. 10A). When a certain number
of positive ions enter, the neuron releases dop-
amine from its other end, which provides the
pleasurable feelings associated with smoking.
When a smoker increases the number of
cigarettes smoked, the number of nicotinic
receptors increases. This happens because of
the way that the nicotine binding impairs the
recycling of receptor proteins, so receptors are
produced faster than they are taken apart. After
a period of steady nicotine exposure, many of
the receptors malfunction and no longer admit
the positive ions that trigger the nerve impulse.
This may be why as time goes on it takes more
nicotine to produce the same effects—a hall-
mark of addiction.
10.5
CLINICAL APPLICATION
Drug Addiction
Receptor
Ion channel
Cigarette
Outside
nerve cell
Membrane
lipid bilayer
Inside
nerve cell
α
protein
subunit
β
protein
subunit
Nicotine
+
+
FIGURE 10A
Nicotine binds and transiently alters postsynaptic receptors that normally bind
the neurotransmitter acetylcholine. As a result, positive ions enter the cell, triggering dopamine
release. With frequent smoking, receptors accumulate and soon become nonfunctional.
Nicotine’s eF
ects on the nervous system are complex.
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