Page 93 - Pagetit

NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

withdrawal syndrome lasts 5 to 7 days. Benzodiazepines are usually used
to lessen the severity of alcohol withdrawal, because of their actions on the
GABA-A receptors.

Neurobiological adaptations to prolonged use
Chronic alcohol consumption can induce alterations in most if not all brain
systems and structures. In animals and humans, specific alterations occur in
the function and morphology of the diencephalon, medial temporal lobe
structures, basal forebrain, frontal cortex and cerebellum, while other
subcortical structures, such as the caudate nucleus, seem to be relatively
unaffected (see Chapter 2). The neuropathological alterations in
mesencephalic and cortical structures are correlated with impairments in
cognitive processes. In people who are dependent on alcohol, the prefrontal
cortex seems particularly vulnerable to the effects of ethanol. Due to the role
of these cortical structures in cognitive functions and in the control of
motivated behaviour, functional alterations in this area of the brain may have
an important part to play in the onset and development of alcohol
dependence (Fadda & Rossetti, 1998). There is a loss in brain volume and
impairment of function that worsens with continued alcohol consumption,
but may be partially reversed after a period of complete abstinence. After
prolonged use of alcohol, impairment of pre-frontal cortex functions, due to
neuronal lesion, may compromise decision-making and emotion, inducing
a lack of judgement and loss of control in reducing alcohol use (Pfefferbaum
et al., 1998). These cognitive impairments need to be readdressed during
alcohol dependence treatment.
Pharmacological treatment of alcohol dependence
Acamprosate (calcium acetyl-homotaurine) is a synthetic drug with structural
similarity to a naturally occurring amino acid. Acamprosate acts centrally
and appears to restore the normal activity of glutaminergic neurons, which
become hyperexcited as a result of chronic exposure to alcohol. Acamprosate
has been available on prescription in France since 1989 and is now available
in many other countries throughout the world. Overall, patients treated with
acamprosate exhibit a significant increase in rate of completion of treatment,
time to first drink, abstinence rate and/or cumulative duration of abstinence,
than patients treated with placebo (Mason, 2001).
The opioid antagonist naltrexone is also effective in reducing relapse and
in helping people to remain abstinent and to decrease alcohol consumption
(Streeton & Whelan, 2001).
Disulfiram is known as a “deterrent” medication because it makes the
ingestion of alcohol unpleasant by altering the body’s normal metabolism of
alcohol. Disulfiram inhibits aldehyde dehydrogenase, the enzyme that
converts acetaldehyde to acetate, thus reducing the clearance of acetaldehyde
from the body. High acetaldehyde levels produce an unpleasant reaction (see

72

Chapter_4 72 19.1.2004, 11:42