Human Physiology, 14th edition (2016)

The Nervous System 193

human twins separated at birth and reared in different envi-

ronments, and other studies involving the use of rats, have

implicated the gene that codes for one subtype of dopamine

receptor (designated D 2 ) in alcoholism. Other addictive

drugs, including cocaine, morphine, and amphetamines, are

also known to activate dopaminergic pathways. Studies dem-

onstrate a decrease in D 2 dopamine receptors in the brains of

addicted subjects.

Addictive drugs promote the activity of dopaminergic

neurons that arise in the midbrain and terminate in the nucleus

accumbens (chapter 8; see fig. 8.21), a collection of neurons

in the ventral striatum that function as part of the limbic sys-

tem (chapter 8; see fig. 8.15). Interestingly, nicotine also pro-

motes the release of dopamine by axons that terminate in this

very location. This suggests that the physiological mechanism

for nicotine addiction in smokers is similar to that for other

abused drugs.

The first generation of drugs used to treat schizophrenia act

as antagonists of the D 2 dopamine receptor, and thereby cause

side effects resembling Parkinson’s disease. This explains why

people with Parkinson’s disease may develop symptoms of

schizophrenia if treated with too much l-dopa. Newer drugs,

called atypical antipsychotic drugs, target many receptors,

including those for norepinephrine, serotonin, and histamine,

and their efficacy suggests that other monoamine neutrotrans-

mitters also contribute to schizophrenia.

Nigrostriatal Dopamine System

The cell bodies of the nigrostriatal dopamine system are
located in a part of the midbrain called the substantia nigra
(“dark substance”) because it contains melanin pigment. Neu-
rons in the substantia nigra send fibers to a group of nuclei
known collectively as the corpus striatum because of its striped
appearance—hence the term nigrostriatal system. These
regions are part of the basal nuclei —large masses of neuron
cell bodies deep in the cerebrum involved in the initiation of
skeletal movements (chapter 8). Parkinson’s disease is caused
by degeneration of the dopaminergic neurons in the substantia
nigra. Parkinson’s disease is the second most common neurode-
generative disease (after Alzheimer’s disease) and is associated
with such symptoms as muscle tremors and rigidity, difficulty
in initiating movements and speech, and other severe motor
problems. Patients are often treated with l-dopa and MAO
inhibitors in an attempt to increase dopaminergic transmission
in the nigrostriatal dopamine system.

Mesolimbic Dopamine System

The mesolimbic dopamine system involves neurons that
originate in the midbrain and send axons to structures in the
forebrain that are part of the limbic system (see fig. 8.21).
The dopamine released by these neurons may be involved in
behavior and reward. For example, several studies involving

Figure 7.31 Norepinephrine action requires G-proteins. The binding of norepinephrine to its receptor causes the
dissociation of G-proteins. Binding of the alpha G-protein subunit to the enzyme adenylate cyclase activates this enzyme, leading to
the production of cyclic AMP. Cyclic AMP, in turn, activates protein kinase, which can open ion channels and produce other effects.

2. G-protein
   subunits
   dissociate

Phosphorylates

proteins

Plasma membrane

Opens

ion channels

AT P

Protein kinase

(inactive)

Protein kinase

(active)

cyclic AMP

4. cAMP activates protein
   kinase, which opens ion
   channels

α

β

γ

α α

Adenylate cyclase

Norepinephrine

Ion channel

Receptor

1. Norepinephrine
   binds to its
   receptor
   3. Adenylate
   cyclase
   G-proteins activated

Postsynaptic cell