Page 89 - Pagetit

NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

— development of tolerance and withdrawal;
— neurological adaptations (direct effects and indirect effects) due to
prolonged use;
— information on pharmacological treatment approaches for each drug
class where available.
Animal models are frequently employed in order to better understand the
biological basis of drug use and drug action. The following animal models
show reliability when used to study selective aspects of human dependence
and substance use:
— self-administration;
— intracerebral self-stimulation;
— place preference;
—drug discrimination.
There are several different procedures within each one of these models, as
extensively reviewed by Koob (1995). The reinforcing properties of the drugs
will cause animals from different species to perform operant tasks to self-
administer drugs. This is considered to model the dependence-producing
potential of the drugs, and is also widely used for preclinical assessment of
new therapies. Self-stimulation of certain brain areas activates brain circuits
that are probably activated by natural reinforcers. Psychoactive substances
are tested in this paradigm to verify whether they decrease the reward
threshold and if they influence in the reward and reinforcement processes.
Place preference uses a Pavlovian conditioning procedure to evaluate
reinforcement by a drug. One assumes that an animal that chooses to spend
more time in an area that has been paired with a certain drug state expresses
the positive reinforcement experience in that location. The last model, i.e.
drug discrimination, relies on the assumption that the discriminative
stimulus of a drug in animals is a reflection of the subjective effects of the
drug in humans. These drug effects would serve as an internal cue that
induces effects similar to the effects of a well-known psychoactive drug.
Research into dependence has been difficult for neuroscientists for the
reason that dependence is made up of many behavioural and physiological
components, some of which can be readily measured, such as withdrawal
symptoms, while others are more difficult to study experimentally, such as
craving and loss of control.
Animal models have been very useful for studying substance use, and the
short-term and long-term physical effects of substance use. Other
components of dependence are more difficult to study, or are uniquely
human, such as craving, social consequences of substance use, and feelings
of loss of control over substance use. However, developments in neuroscience
over the past several years have greatly enhanced the ability to study changes
in human brain function and composition, using functional magnetic

68

Chapter_4 68 19.1.2004, 11:42