anding of neurotransmission by learning how
different drugs of abuse disrupt communication between neurons. Students
then conduct an activity investigating the effect of caffeine on their heart rate.
Finally, students analyze data on how the way a drug is taken into the body
influences its effect.
Major Concept
Drugs affect the biology and chemistry of the brain.
Objectives
By the end of these activities, the students will
understand that certain drugs interfere selectively with neurotransmission, and
realize that the effect of a drug is dependent upon dosage and route of
administration.
Basic ScienceHealth Connection
Drugs of abuse are valuable tools for investigations of brain function because
they can mimic or block actions of neurotransmitters, and thus exert effects on
homeostasis and behavior.
From: Principles of Neural Science, Third edition, Eric R.
Kandel, James H. Schwartz, Thomas M. Jessell �The
McGraw-Hill Companies. (m = mitochondria)
At a Glance
57
The Brain: Understanding Neurobiology Through the Study of Addiction
Background
Information
Drugs Disrupt Neurotransmission
How do drugs cause their effects on the brain and behavior? Lesson 1 intro�
duced students to the idea that a specific brain region, the reward system (part
of the limbic system), regulates feelings of pleasure and that this region is acti�
vated by drugs of abuse. But what do drugs actually do in that brain region?
Drugs interfere with neurotransmission. More specifically, drugs of abuse pro�
duce feelings of pleasure by altering neurotransmission by neurons in the
reward system that release the neurotransmitter dopamine.
1, 2
Thus, drugs of
abuse alter the communication between neurons that is mediated by dopamine.
Because the synapse is so complex, there are a variety of sites at which drugs
may affect synaptic transmission. One way to affect synaptic transmission is to
increase the amount of neurotransmitter that is released into the synaptic space.
Drugs like alcohol, heroin, and nicotine excite the dopamine-containing neu�
rons in the ventral tegmental area (VTA) so that they produce more action
potentials.
1, 2
As the number of action potentials increases, so does the amount
of dopamine released into the synapse. Amphetamines (e.g., methampheta�
mine, crystal, crank) actually cause the release of dopamine from the vesicles.
This is independent of the rate of action potentials and, depending on dose, can
cause a relatively quick and prolonged rise of extracellular dopamine levels.
Figure 3.1: Methamphetamine alters dopamine neurotransmission in two ways. Methamphetamine
enters the neuron by passing directly through nerve cell membranes. It is carried to the nerve cell
terminals by transporter molecules that normally carry dopamine or norepinephrine. In the nerve
terminal, methamphetamine enters the dopamine- or norepinephrine-containing vesicles and
causes the release of neurotransmitter. Methamphetamine also blocks the dopamine transporter
from pumping dopamine back into the transmitting neuron. Methamphetamine acts similarly to
cocaine in this way.
Nicotine not only acts at the cell body in the VTA to increase the number of
action potentials and number of vesicles released from a neuron, but it also acts
by another mechanism to alter dopamine release. When nicotine binds to nico�
tine receptors on the dopamine-containing axon terminals in the nucleus
accumbens, more dopamine is released with each action potential.
1
58
Lesson 3
Figure 3.2: Nicotine binds to specific receptors on the presynaptic neuron. When nicotine binds to
receptors at the cell body, it excites the neuron so that it fires more action potentials (electrical sig�
nals) that move toward the synapse causing more dopamine release (not shown in figure). When
nicotine binds to nicotine receptors at the nerve terminal (shown above), the amount of dopamine
released in response to an action potential is increased.
Drugs may also alter synaptic transmission by directly affecting the postsynap�
tic receptors. Some drugs activate receptors and others block them.
While THC (the main psychoactive chemical in marijuana) and morphine acti�
vate their specific receptors, other drugs block specific receptors. Caffeine, the
mild stimulant found in coffee and some soft drinks, exerts its effects by pre-
venting a neurotransmitter/neuromodulator called adenosine from binding to
its receptor. Normally, the binding of adenosine to its receptor causes sedation;
it is a natural sleep-inducer. Instead of causing sedation, the blocking of the
adenosine receptors with caffeine leads to an increase in activity and arousal
levels.
1, 3
The actions of some drugs are very complex. LSD, for example, acts on sero�
tonin receptors. Serotonin, an important neurotransmitter in many brain
regions, is involved in regulating a wide variety of functions, including mood
and basic survival functions such as sleep and eating. Scientists continue to
study how hallucinogens act, but apparently LSD activates some serotonin
receptors (LSD acts as a receptor agonist) and blocks other serotonin receptors
(LSD acts as a receptor antagonist).
1
A third way to affect synaptic transmission is to alter the removal of neuro�
transmitters from the synapse. Cocaine and amphetamines work this way (this
is the second way in which amphetamines can alter neurotransmission).
1, 3
Both
drugs block the dopamine transporter (reuptake pump) that removes
dopamine from the synapse. The result is a fairly rapid rise of dopamine in the
synapse, leading to feelings of euphoria and well-being. There are no drugs of
abuse that block enzymatic destruction of neurotransmitters, although some
antidepressants work by this mechanism.
59
The Brain: Understanding Neurobiology Through the Study of Addiction
Figure 3.3: When cocaine enters the brain, it blocks the dopamine transporter from pumping
dopamine back into the transmitting neuron, flooding the synapse with dopamine. This intensi�
fies and prolongs the stimulation of receiving neurons in the brains pleasure circuits, causing a
cocaine high.
Drugs of abuse share a common action: they act on the brains reward system.
Within that system, they all (except perhaps for LSD) share the ability to
increase the levels of dopamine in the nucleus accumbens. This almost certainly
accounts for the rewarding (pleasurable) effects of abused drugs.
The effects of drugs are not limited to the reward pathway in the brain. Drugs can
act in various regions of the brain to exert their effects, but their ability to alter
dopamine neurotransmission in the ventral tegmental area (VTA) and the nucleus
accumbens is one of the most important factors that drives continued drug use.
Drugs Mimic Natural Body Chemicals
The ability of drugs to interrupt normal synaptic transmission may seem odd. After all, if receptors have such great
specificity for a single type of binding partner, how can drugs disrupt the process? The answer lies in the similarity
in conformation, or structure, of the drugs to natural body chemicals. For example, the receptors that bind mor�
phine and other opiates are expressed in the brain to recognize natural opioid peptides called endorphins and
enkephalins that are made by our brains and used as neurotransmitters.
4
It is an evolutionary coincidence that
these receptors recognize a plant-derived chemical (drug) as well. This coincidence is a double-edged sword. Opi�
ate compounds that come from plants are both the most potent analgesics (pain relievers) available and some of
the most potent addictive drugs as well. Morphine continues to be one of the most effective drugs to relieve the
pain associated with many chronic diseases. The doses of opiates used by addicts simply overwhelm the opiate
receptors in the VTA and nucleus accumbens and cause profound feelings of pleasure (euphoria). Tetrahydro�
cannabinol (THC), the active ingredient in marijuana, binds to receptors in the brain that are specific for anan�
damide, an endogenous chemical that is similar in structure to THC. Because THC is similar in structure to
anandamide, it binds to the same receptor. Scientists do not yet fully understand anandamides function in the
body, but it may play a role in memory functions. Marijuana disrupts short-term memory in humans. Anandamide
may be involved in eliminating unneeded information from memory, but much remains to be learned before its
functions are understood. Other studies indicate anandamine in an area of the brain called the dorsal striatum
inhibits movements that are stimulated by dopamine.
5
This finding may enable scientists to develop medications
for treating diseases such as schizophrenia, Gilles de la Tourette syndrome, or Parkinsons disease. Each of these
diseases involves dopamine imbalances in the brain.
60
Lesson 3
The Dose Changes the Drugs Effects
For drugs to exert their effects, a person must take them into the body and
absorb them into the bloodstream. Some of these effects relate to the amount
of the drug taken. For example, at low doses no effect (or response) can be
observed or measured. Once a certain amount of the drug enters the blood-
stream, a response can then be measured. This point is known as the threshold.
At doses of the drug below the threshold amount, there is too little of the
drug in the body to cause neurons to be activated. For example, there may
not be enough heroin in the body to bind to opiate