Mechanisms of Addiction:
A Short Review
Yanis AFIR
Abstract
Addiction is a major issue facing every country around the world. Over half a century, many research-
es have been conducted in order to understand the molecular mechanisms underlying this phenom-
enon, hoping to find a proper treatment. In this very short and very superficial review, we will try to
highlight the cardinal points of the current theories regarding the mechanisms of addiction. We will
discuss the major concepts and the established ideas only, avoiding all the points of controversy and
conflict. Furthermore, we will not discuss the addiction to Nicotine and Alcohol, as each deserves
its own article. Finally, we will have few words on some of the unconventional forms of addiction.
Introduction
T
he term “drug abuse ” refers to the use of drugs
outside of medical supervision and in a manner
that is potentially harmful or illegal 1 . Drug ad-
diction or « substance dependence », a preferred term,
is defined by the World Health Organization and the
American Psychiatric Association as a compulsive drug
use despite significantly negative consequences 2 .
Addiction is one of today’s biggest health
problems worldwide, causing the death of millions of
people each year. In Algeria, a national study in 2010
identified over 300 000 cases of addiction throughout
the country, among them, 60% were between 20 and
30 years old 3 .
Neuroanatomical substratum: Reward circuit and
the role of dopamine
For surviving purposes, our brain has mastered the
ability to collect, synthesize and summarize the var-
ious surrounding information and interpret them ac-
cording to their utility or danger. Any kind of gratifi-
cation is translated into a “reward” signal in our brain
providing euphoria and pleasure. These rewards can
be physical, sensorial or emotional.
Anatomically speaking, both natural rewards
and addictive drugs activate the same system: they
stimulate the release of dopamine from neurons
of the presynaptic ventral tegmental area into the
proximal part of the striatum, called the nucleus ac-
cumbens. This process involves a specific reward cir-
cuit described in many neuroanatomy textbooks, and
summarized in figure 1.
The first consequence of these statements is
that, to be addictive, a drug has to act on the dopa-
mine release. Although many authors 6 and studies
challenge this long-lasting dogma, generally speak-
ing, psychotropic drugs that do not produce significant
dopamine release in the nucleus accumbens are not
addictive.
The classic theory of dopamine suggests that
the cause of addiction is the human nature of seek-
ing short-term pleasure despite long-term negative
effects. Yet, this principle hardly explains the long per-
sistence of drug addiction as the problems and neg-
ative effects grow bigger and surpass the short-term
pleasure. Latest researches demonstrated that addic-
tion is not simply an act of the “hedonic molecule” but
rather involves multiple actors such as dysfunction of
neuronal circuits, alteration of higher functions, mem-
ory and reinforcement and neural plasticity.
Schultz & al 9 demonstrated that dopaminergic
neurons have a changing pattern of responses to re-
wards. In an experiment, monkeys have been trained
to receive juice (the reward) at a fixed interval. A slight
and transient increase in dopamine levels was ob-
served each time the reward was given.
After that, visual or auditory signals (called
cues) were presented to monkeys right before the re-
ward. As monkeys understood that the cues predicted
the juice, the dopamine levels no longer responded to
the juice but rather earlier, in response to the predic-
tive cue. Interestingly, if the cue was presented but the
reward withheld, firing paused at the time the reward
was expected. In opposite, if the reward was unexpect-
ed, because appearing without a prior cue, or exceed-
ed expectation, firing rate was enhanced.
These results suggest that dopamine serves as
a “prediction-error signal”, where an increase in dopa-
mine level would signify a reward (or reward-related
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