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4. PSYCHOPHARMACOLOGY OF DEPENDENCE FOR DIFFERENT DRUG CLASSES

resonance imaging (MRI), regional cerebral blood flow, and positron emission
tomography (PET).
Major advances in the understanding and treatment of dependence have
come from understanding the basic mechanisms of drug action and long-
term health consequences. There have been some successful treatments,
such as methadone for heroin dependence, nicotine patches for nicotine
dependence, and various pharmacotherapies for alcohol dependence.
The development of treatments and medications is promising, but brings
with it a host of ethical issues which need to be addressed (see Chapter 7).
However, it is important to first understand the biology behind these new
approaches to treatment, as well as the research and animal models used to
gain insight into the effects of psychoactive substance use.

Alcohol (ethanol)

Introduction
Beverage alcohol (ethyl alcohol or ethanol) is consumed throughout the world
for recreational and religious purposes (Jacobs & Fehr, 1987). It is produced
by fermentation and distillation of agricultural products.
Ethanol is almost always taken orally, and absorbed quickly from the small
intestine into the bloodstream. Delays in gastric emptying, caused by, for
example, the presence of food, will slow its absorption. First-pass metabolism
by gastric, and consequently hepatic alcohol dehydrogenase, decreases the
bioavailability of ethanol while gender and genetic diversity may account for
individual differences in blood alcohol levels. Very small amounts of ethanol
may be excreted unchanged in urine, sweat and breath while most of it is
metabolized to acetyldehyde by alcohol dehydrogenase, catalase and
microsomal P450 enzymes largely in the liver. Subsequently, acetaldehyde is
converted to acetate by hepatic aldehyde dehydrogenase. As discussed in
Chapter 5 the effects of ethanol differ widely between individuals because of
genetic variation in these metabolic enzymes. This may contribute to the fact
that some people are more prone than others to the development of alcohol
dependence.

Behavioural effects
In humans, the acute behavioural effects of ethanol vary between individuals
according to many factors such as dose, rate of drinking, gender, body weight,
blood alcohol level and the time since the previous dose. Ethanol has biphasic
behavioural effects. At low doses, the first effects that are observed are
heightened activity and disinhibition. At higher doses, cognitive, perceptual
and motor functions become impaired. Effects on mood and emotions vary
greatly from person to person (Jacobs & Fehr, 1987).
Ethanol is self-administered orally by animals. Rats selectively bred for
high preference for ethanol will reliably self-administer ethanol by free-choice

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