Page 364 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Dependence, Addiction
Dependence or rather addiction is an acquired get worse the longer the drug addiction had
compulsion that dictates the behavior of those lasted. Withdrawal symptoms lead to physical
who are dependent or addicted. In drug de- dependence in the addict. Psychological de-
pendence there is a great craving for the pendence is the result of the need for the posi-
particular drug. For the dependent person, ob- tive effects of the drug and/or the fear of the
Systems taining and supply of the drug become priori- neurobiological or psychological withdrawal
ties over all other kinds of behavior. Among the
symptoms (→ A). The desire for the positive ef-
fects remains after the withdrawal symptoms
most important of such drugs are nicotine, al-
have abated. Stress, among other factors, fa-
cohol, opiates, and cocaine. There are, how-
Neuromuscular and Sensory ing pills [hypnotics] and analgesics) that can pathways (→ A; see also p. 352) apparently
ever, also many other drugs (especially sleep-
vors relapse.
Mesolimbic and mesocortical dopaminergic
lead to dependence.
play an important role in the development of
It is not only the supply of the particular
dependence or addiction. By activating these
drug that is important in the development of
addiction, as only some of those who take a
pathways, for example, with alcohol or opi-
ates, the addict tries to produce a feeling of
drug become dependent. Of great significance
for the development of addictive behavior is a
wellbeing or euphoria or, conversely, to pre-
drawing the substance the activity of the do-
that in those dependent on alcohol or cocaine,
certain polymorphisms of the gene for the do-
paminergic system is reduced or the target
10 genetic disposition (→ A). It has been shown vent dysphoria. It is possible that on with-
pamine transporter (DAT-1) are especially
cells are less sensitive. Withdrawal symptoms
common. Genetic defects of acohol dehydro- can be attenuated by activating endorphiner-
genase (ADH) or acetaldehyde dehydrogenase gic, GABAergic, dopaminergic, or serotoniner-
(ALDH) impair the breakdown of alcohol and gic receptors.
thus increase its toxic effect. These enzyme de- The cellular mechanisms of tolerance have
fects therefore protect against alcohol depen- been in part elucidated for opiates. Stimulation
dence. The attempt has been made to achieve of the receptors leads to phosphorylation via G
pharmacological inhibition of ALDH (with de- protein receptor kinases and thus to the inacti-
sulfiram) in order to force an increase in acet- vation of the receptor (→ C). The receptors are
aldehyde and thus stop addictive behavior also internalized. The effectiveness of receptor
through the toxic effect of acetaldehyde (nau- stimulation can also be reduced by influencing
sea, vomiting, hypotension). Because of the cellular signal transmission. The opiate recep-
high risk and relatively limited success this ap- tor acts partly via inhibition of adenylylcyclase
proach has now been abandoned. (AC), a decrease of cyclic adenosine mono-
Another important factor in dependence is phosphate (cAMP) and reduced activation of
the social context (→ A). Thus, a change in so- protein kinase A (→ D). Taking opiates thus at
cial environment can make it easier to give up first diminishes cAMP formation (→ E2).
drugs. Most of the soldiers, for example, who Chronic intake, however, raises the expression
took drugs during the Vietnam War were not of adenylylcyclase by influencing cAMP-re-
addicted after their return to the USA. sponsive element-binding protein ([CREB]
Frequently addicts develop a tolerance to → p. 6ff.). As a result, even in the presence of
the substance and the initial effect gradually opiates, cAMP is still formed (→ E3). Subse-
weakens if drug intake continues (→ A,B). If quent withdrawal of opiates will, for example,
intake is suddenly discontinued, there is a re- via a massive increase in cAMP (→ E4), lead to
versal of effect (→ B). Chronic intake weakens withdrawal symptoms.
the effect of the drug and increases the rever-
sal effect on discontinuance. If the addict
wants to attain the same effect, the dosage
354 has to be increased. When the drug is discon-
tinued, withdrawal symptoms develop that
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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