ADDICTION
THEORIES AND MECHANISMS
1
Presenter: Imran Jamal
OUTLINE

Definition

Theories of addiction

Incentive sensitization theory

Molecular and cellular basis of addiction

Animal models of addiction

Future directions
2
DEFINITION

Addiction is a behaviour over which an individual
has impaired control with harmful consequences
3
LIFECYCLE OF ADDICTION
4
THEORIES OF ADDICTION

Early theories
Consume
substance
Agent produces
hedonic effect
=reward
Development
of dependence
Recurrent
drive for
reward
5
THEORIES OF ADDICTION

Theories focussing on conceptualization and
general processes.

Theories focussing on effects of addictive stimuli.

Theories focussing on individual susceptibility.

Theories focussing on environmental factors.

Theories focussing on recovery and relapse
6
CONCEPTUALIZATION AND GENERAL
PROCESSES

Behavioural and social theories




Loss-grief addiction model
Artificially-induced drive
Compulsive behaviour
Biological theories



Biochemical mechanisms
Receptor-enzyme systems
Evolutionary game theory and multiple chemical
sensitivity
7

Theories focussing on conceptualization and
general processes.

Theories focussing on effects of addictive stimuli.

Theories focussing on individual susceptibility.

Theories focussing on environmental factors.

Theories focussing on recovery and relapse
8
EFFECTS OF ADDICTIVE STIMULI

Why do particular stimuli have a high propensity
to becoming a focus of addiction?

Such stimuli: pleasure, relief or excitement.

Incentive sensitization theory.

Dominant theme: Positive and negative
reinforcing properties of drugs.
9

Theories focussing on conceptualization and
general processes.

Theories focussing on effects of addictive stimuli.

Theories focussing on individual susceptibility.

Theories focussing on environmental factors.

Theories focussing on recovery and relapse
10
INDIVIDUAL SUSCEPTIBILITY

Genetic susceptibility

Personality

Social factors
11

Theories focussing on conceptualization and
general processes.

Theories focussing on effects of addictive stimuli.

Theories focussing on individual susceptibility.

Theories focussing on environmental factors.

Theories focussing on recovery and relapse
12
ENVIRONMENTAL FACTORS AND SOCIAL
CONDITIONS

Stressors

Social roles

Economic factors
13

Theories focussing on conceptualization and
general processes.

Theories focussing on effects of addictive stimuli.

Theories focussing on individual susceptibility.

Theories focussing on environmental factors.

Theories focussing on recovery and relapse.
14
RECOVERY AND RELAPSE

Conditioning

Psychosocial factors

Transtheoretical model
15
INCENTIVE SENSITISATION THEORY
liking
Long-lasting
changes in brain
organisation
Incentive motivation
and reward systems of
brain altered
Potentially
addictive drugs
Critical
neuroadaptations
for addiction
INCENTIVE
SENSITIZATION
THEORY
Mediate a
subcomponent of reward
(wanting)
Hypersensitive brain
reward systems
Drugs and drugassociated stimuli
Susceptible to relapse
+
Persistence of
sensitization
16
MOLECULAR AND CELLULAR BASIS

Upregulation of the cyclic AMP pathway



Adaptations in receptor-G protein coupling



Increased adenyl cyclase and prot. Kinase A
concentrations
Seen in the locus coeruleus, nucleus accumbens,
ventral tegmental area and periaqueductal gray.
Receptor phosphorylation (GRKs)
Adaptations in abundance of G protein subunits
Longer lasting molecular and cellular adaptations



Changes in gene expression
Transcription factors (FRAs)
Adaptation in Glutamatergic transmission (enhanced
AMPA receptor stimulation
17
ANIMAL MODELS OF ADDICTION

Intracranial self-stimulation (ICSS)

Conditioned place preference (CPP)

Behavioural sensitization andself-administration
paradigms
18
ICSS

Implant electrical electrodes on certain brain
areas

Electrical stimulation

Response

Drugs of abuse reduce ICSS thresholds

Used for assessment of changes or dysregulation
in the basic hedonic state of animal after chronic
drug exposure
19
ICSS
20
ANIMAL MODELS OF ADDICTION

Intracranial self-stimulation (ICSS)

Conditioned place preference (CPP)

Behavioural sensitization and self-administration
paradigms
21
CPP

Initially, animal exposed to 2 environments with
different stimulus modalities.
Drug pre-Rx
 Vehicle pre-Rx

Environment A
Environment B
Environment A

No Rx
22
Environment B
CPP
23

Intracranial self-stimulation (ICSS)

Conditioned place preference (CPP)

Behavioural sensitization and self-administration
paradigms
24
BEHAVIOURAL SENSITIZATION AND
SELF ADMINISTRATION PARADIGM




Bhvral sensitization: Progressive increase in the
motor stimulatory effects of a drug following repeated
intermittent administration.
Drug ‘liking’
Drug ‘wanting’
Self-administration: most widely used model
Animals trained to perform an operant behaviour to
receive a drug reinforcer.
25
BEHAVIOURAL SENSITIZATION AND
SELF ADMINISTRATION PARADIGM
26
FUTURE DIRECTIONS IN RESEARCH




Greatest gap in knowledge: identification of the
long-lived adaptations
Animal models of relapse esp. stress induced
relapse
Transgenic and knockout methodologies
Detailed understanding of molecular and cellular
mechanisms of addiction:

Basis of new medical treatments of addictive
disorders
27