11
Te important idea to keep in mind is this: Te function of
a neurotransmitter is determined by the receptor to which it
binds.
Effects: Excitatory Versus Inhibitory
Some neurotransmitters are excitatory (cause depolarization).
Some are inhibitory (cause hyperpolarization). Others ex-
ert both effects, depending on the specific receptor types with
which they interact.
For example, the amino acids GABA and glycine are usually
inhibitory, whereas glutamate is typically excitatory (±able 11.3).
On the other hand, ACh and NE each bind to at least two recep-
tor types that cause opposite effects. For example, acetylcholine
is excitatory at neuromuscular junctions in skeletal muscle and
inhibitory in cardiac muscle.
Actions: Direct Versus Indirect
Neurotransmitters that act
directly
are those that bind to and
open ion channels. Tese neurotransmitters provoke rapid re-
sponses in postsynaptic cells by altering membrane potential.
ACh and the amino acid neurotransmitters are typically direct-
acting neurotransmitters.
418
Sex! Drugs!
Rock ‘n’ roll! Eat, drink,
and be merry! Why do we find these
activities so compelling? Our brains are
wired to
reward
us with
pleasure
when we engage in behavior that is
necessary for our own and our species’
survival
. This reward system consists of
dopamine-releasing neurons in areas of
the brain called the
ventral tegmental area
(VTA), the
nucleus accumbens
, and the
amygdala
.
Our ability to “feel good” involves
brain neurotransmitters in this reward
system. For example, the ecstasy of
romantic love may be just a brain bath
of glutamate and norepinephrine, which
act on the reward system to release
dopamine.
Unfortunately, drugs of abuse can
subvert this powerful system. The 1930s
songwriter Cole Porter knew what he
was talking about when he wrote “I
get a kick out of you,” because these
neurotransmitters are chemical cousins
of the amphetamines. People who use
“crystal meth” (methamphetamine)
artificially stimulate their brains to provide
their highly addictive pleasure flush.
However, their pleasure is short-lived,
because when the brain is flooded with
neurotransmitter-like chemicals from the
outside, it makes less of its own (why
bother?).
Cocaine, another reward system
titillater, has been around since ancient
times. Once a toy of the rich, its granular
form is inhaled, or “snorted.” The laws
of supply and demand have now brought
cheaper cocaine to the masses, notably
“crack”—a cheaper, more potent,
smokable form of cocaine. For $50 or so,
a novice user can experience a rush of
intense pleasure. But crack is treacherous
and intensely addictive. It produces not
only a higher high than the inhaled form
of cocaine, but also a deeper crash that
leaves the user desperate for more.
How does cocaine produce its effects?
Basically, the drug stimulates the reward
system and then “squeezes it dry.”
Cocaine produces its rush by hooking up
to the dopamine reuptake transporter
protein, blocking the reabsorption
of dopamine. The neurotransmitter
remains in the synapse and stimulates
Pleasure Me, Pleasure Me!
the postsynaptic receptor cells again and
again, allowing the body to feel its effects
over a prolonged period. This sensation is
accompanied by increases in heart rate,
blood pressure, and sexual appetite.
As repeated doses of cocaine continue
to block dopamine uptake, the body
releases less and less dopamine and the
reward system effectively goes dry. The
cocaine user becomes anxious and, in a very
real sense, unable to experience pleasure
without the drug. The postsynaptic cells
A
C L O S E R
LOOK
Normal
Abuser:
10 days
without
cocaine
Abuser:
100 days
without
cocaine
PET scans show that normal levels of brain activity (yellow and red) are depressed in
cocaine users long after they stop using the drug.
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