Title: DRUG ADDICTION AND REWARD
1DRUG ADDICTION AND REWARD
- 60 MILLION PEOPLE ADDICTED TO NICOTINE, ALCOHOL
OR BOTH. - 5.5 MILLION PEOPLE ARE ADDICTED TO ILLEGAL DRUGS.
- 4 MILLION ARE ADDICTED TO PRESCRIPTION DRUGS.
2FIVE COMMONLY ABUSED DRUGS
- TOBACCO
- NEXT TO CAFFEINE, TOBACCO IS THE MOST WIDELY
ABUSED DRUG IN OUR SOCIETY. - NICOTINE IS THE MAJOR PSYCHOACTIVE INGREDIENT OF
TOBACCO.
3TOBACCO
- CONSIDERABLE TOLERANCE DEVELOPS TO SOME OF THE
IMMEDIATE ADVERSE EFFECTS OF TOBACCO. - -NON-SMOKER.
- -SMOKER.
4TOBACCO
- HEAVY SMOKERS WHO STOP SMOKING CAN EXPERIENCE
- DEPRESSION, ANXIETY, RESTLESSNESS, IRRITABILITY,
CONSTIPATION, DIFFICULTIES IN SLEEPING AND
CONCENTRATION.
5LONG-TERM TOBACCO USE
- SMOKERS SYNDROME--CHEST PAIN, LABORED BREATHING,
WHEEZING, COUGHING, INCREASED SUSCEPTIBILITY TO
INFECTIONS OF THE RESPIRATORY TRACT. - LETHAL LUNG DISORDERS--PNEUMONIA, BRONCHITIS,
EMPHYSEMA, LUNG CANCER.
6LONG-TERM TOBACCO USE
- OTHER CANCERS--MOUTH, THROAT, KIDNEYS, PANCREAS,
BLADDER AND STOMACH. - CARDIOVASCULAR DISEASE--CULMINATING IN HEART
ATTACK OR STROKE.
7ALCOHOL
- APROXIMATELY 2/3 OF THE POPULATION CONSUME
ALCOHOLIC BEVERAGES. - OF THESE, 15 MILLION ARE ADDICTED.
8ALCOHOL
- MODERATE DOSES--COGNITIVE, PERCEPTUAL, VERBAL AND
MOTOR IMPAIRMENT. - CAN ALSO LEAD TO INTERESTING BEHAVIORS IN SOCIAL
SITUATIONS.
9ALCOHOL
- HIGH DOSES--UNCONCIOUSNESS AND RISK OF DEATH FROM
RESPIRATORY DEPRESSION.
10ALCOHOL WITHDRAWAL
- 5 OR 6 HOURS AFTER CESSATION OF A LONG BOUT OF
DRINKING. - -SEVERE TREMORS, AGITATION, HEADACHE, NAUSEA,
VOMITING, ABDOMINAL CRAMPS, PROFUSE SWEATING AND
HALLUCINATIONS.
11ALCOHOL WITHDRAWAL
- 15-30 HOURS.
- -CONVULSIVE ACTIVITY.
12ALCOHOL WITHDRAWAL
- 2-3 DAYS.
- DELERIUM TREMENS (DTs).
- DISTURBING HALLUCINATIONS, DELUSIONS, AGITATION,
CONFUSION, HYPERTHERMIA AND RAPID HEARTBEAT.
13CHRONIC ALCOHOL CONSUMPTION
- EXTENSIVE BRAIN DAMAGE.
- CIRRHOSIS OF THE LIVER.
- HEART DAMAGE.
- GI TRACT DAMAGE.
- TRAFFIC FATALITIES.
14ALCOHOL AND DEVELOPMENT
- LIKE NICOTINE, ALCOHOL READILY PENETRATES THE
PLACENTAL MEMBRANE AND AFFECTS THE FETUS. - FETAL ALCOHOL SYNDROME (FAS).
15ALCOHOL HAS MULTIPLE SITES OF ACTION
- CALCIUM CHANNELS.
- GABA RECEPTORS.
- GLUTAMATE RECEPTORS.
- 2ND MESSENGER SYSTEMS.
16MARIJUANA
- THE PSYCHOACTIVE EFFECTS OF MARIJUANA ARE LARGELY
ATTRIBUTABLE TO A CONSTITUENT CALLED THC
(DELTA-9-TETRAHYDROCANNABINOL).
17HAZARDS
- LUNG DAMAGE.
- MORE LIKELY TO DEVELOP CHRONIC BRONCHITIS AND
ASTHMA.
18MECHANISM OF ACTION
- THC BINDS TO RECEPTORS THAT ARE DENSE IN THE
BASAL GANGLIA, HIPPOCAMPUS, CEREBELLUM AND
NEOCORTEX.
19POT AND THE BRAIN
20ENDOGENOUS LIGAND?
- RECENTLY, THE GENE FOR THE THC RECEPTOR HAS BEEN
CLONED. - TRIGGERED RESEARCH FOR AN ENDOGENOUS THC-LIKE
CHEMICAL. - ANANDAMIDE.
21COCAINE
- COCAINE HYDROCHLORIDE.
- USERS REPORT BEING SWEPT AWAY BY A WAVE OF
WELL-BEING. - CONFIDENT, ALERT, ENERGETIC, FRIENDLY, OUTGOING,
FIDGETY, TALKATIVE.
22HAZARDS
- RISK OF SEIZURES, LOSS OF CONCIOUSNESS, DEATH
FROM RESPIRATORY ARREST OR STROKE. - INSOMNIA, TREMORS, NAUSEA AND PSYCHOTIC BEHAVIOR.
23MECHANISM OF ACTION
- EXERTS BEHAVIORAL EFFECT BY FACILITATING
CATECHOLAMINERGIC TRANSMISSION. - HOW?
24OPIATES
- EXTRACTED FROM SAP OF SEEDS FROM THE OPIUM POPPY.
- MORPHINE AND CODEINE.
25OPIATES
- HEROIN IS A SYNTHESIZED OPIATE.
- ADDITION OF 2 ACETYL GROUPS TO THE MORPHINE
MOLECULE.
26OPIATES
- THE EFFECT OF OPIATES MOST VALUED BY OPIATE
ADDICTS IS THE RUSH THAT FOLLOWS IV INJECTION. - OPIATES ARE HIGHLY ADDICTIVE.
27COLD TURKEY?
- SYMPTOMS OF OPIATE WITHDRAWAL HAVE BEEN GREATLY
EXAGGERATED. - MAIN RISKS OF OPIATE ADDICTION ARE INDIRECT.
28MECHANISM OF ACTION
- BIND TO OPIATE RECEPTORS.
- ENDOGENOUS LIGAND?
- ENDORPHINS.
29BIOPSYCHOLOGICAL THEORIES OF ADDICTION
- PHYSICAL-DEPENDENCE THEORY
- POSITIVE-INCENTIVE THEORY
- -PRIMARY REASON MOST ADDICTS TAKE DRUGS IS TO
OBTAIN THE PLEASURABLE EFFECTS OF THE DRUG.
30ROBINSON AND BERRIDGE(1993)
- ARGUE THAT IT ISNT THE PLEASURE OF DRUG TAKING
PER SE THAT IS THE BASIS OF ADDICTION IT IS THE
ANTICIPATED PLEASURE OF DRUG TAKING.
31REWARD CIRCUITS IN THE BRAIN
- OLDS AND MILNER (1954)
- INTRACRANIAL SELF-STIMULATION.
32ICSS
- ANIMALS WILL PERFORM A RESPONSE, SUCH AS PRESSING
A LEVER, IN ORDER TO ADMINISTER BRIEF BURSTS OF
ELECTRICAL STIMULATION TO SPECIFIC SITES IN THEIR
OWN BRAIN.
33ICSS
34OLDS AND MILNER (1954)
- ARGUED THAT THE SPECIFIC BRAIN SITES THAT MEDIATE
SELF-STIMULATION ARE THOSE THE NORMALLY MEDIATE
THE PLEASURABLE EFFECTS OF NATURAL REWARDS (FOOD,
SEX, WATER).
35REWARD CIRCUIT VIEW OF ICSS
- 1) BRAIN STIMULATION THROUGH ELECTRODES THAT
MEDIATE SELF-STIMULATION OFTEN ELICITS NATURALLY
MOTIVATED BEHAVIORS. - 2) INCREASES IN NATURAL MOTIVATION INCREASES
SELF-STIMULATION RATES.
36REWARD CIRCUIT VIEW OF ICSS
- 3) LEVER PRESSING FOR STIMULATION AT SOME BRAIN
SITES IS OFTEN QUITE SIMILAR TO LEVER PRESSING
FOR NATURAL REWARDS.
- Acquisition is slow.
- Response rates are low.
- Extinction is slow.
- Priming not necessary.
37THE DOPAMINE SYSTEM
- THIS ASCENDING NEUROTRANSMITTER SYSTEM PLAYS A
PARTICULARLY IMPORTANT ROLE IN ICSS. - NEURONS OF THIS SYSTEM HAVE THEIR CELL BODIES IN
2 MIDBRAIN NUCLEI. - SUBSTANTIA NIGRA AND THE VENTRAL TEGMENTAL AREA.
38NEUROANATOMICAL NOTE
- SUBSTANTIA NIGRA--gtSTRIATUM (NIGROSTRIATAL
SYSTEM). - VTA--gtLIMBIC AND CORTICAL STRUCTURES
(MESOCORTICAL SYSTEM). - VTA--gtNUCLEUS ACCUMBENS.
39EVIDENCE
- MAPPING STUDIES MANY OF THE BRAIN SITES AT WHICH
ICSS OCCURS ARE PART OF THE DOPAMINE SYSTEM. - CEREBRAL DIALYSIS STUDIES MICRODIALYSIS.
40EVIDENCE
- 3) DOPAMINE AGONIST AND ANTAGONIST STUDIES
- 4) LESION STUDIES
41NEURAL MECHANISMS OF ADDICTION
- TWO BEHAVIORAL PARADIGMS HAVE BEEN USED
EXTENSIVELY IN THE STUDY OF THE NEURAL MECHANISMS
OF ADDICTION
- Drug self-administration paradigm.
- Conditioned-place preference (CPP).
42SELF-ADMINISTRATION
43CPP
44DOPAMINE AND ADDICTION
- LAB ANIMALS SELF-ADMINISTER MICROINJECTIONS OF
ADDICTIVE DRUGS DIRECTLY INTO BRAIN AREAS
INNERVATED BY THE DOPAMINE SYSTEM BUT NOT OTHER
BRAIN AREAS.
45DOPAMINE AND ADDICTION
- INTRACRANIAL INJECTIONS INTO SIMILAR BRAIN AREAS
PRODUCE CPPS. - ADDICTIVE DRUGS INCREASE REWARDING EFFECTS OF
ELECTRICAL STIMULATION.
46DOPAMINE AND ADDICTION
- DISRUPTION OF DOPAMINE SYSTEM WITH SELECTIVE
LESIONS OR ANTAGONISTS REDUCE THE REWARDING
EFFECTS OF ADDICTIVE DRUGS.
47DOPAMINE AND ADDICTION
- IN-VIVO VOLTAMMETRY AND MICRODIALYSIS RECORDINGS
FROM THE NUCLEUS ACCUMBENS HAVE SHOWN THAT
SELF-ADMINISTRATION OF MOST ADDICTIVE DRUGS IS
ASSOCIATED WITH INCREASED DOPAMINE RELEASE.
48MULTIPLE MEMORY SYSTEMS AND DRUG ADDICTION
- This theoretical view focuses on various learning
and memory systems in which the normal functions
of these complex neural circuits become subverted
leading to compulsive drug seeking behaviours. - White, 1996 Everitt et al., 2001.
49MULTIPLE MEMORY SYSTEMS AND DRUG ADDICTION
- Amygdala?acquires information that promotes
approach and interaction with drug associated
stimuli. - Dorsal striatum?promotes the acquisition of
stimulus-response (S-R) habits. - Hippocampus?acquire information about the context
in which drug stimuli are obtained.
50MULTIPLE MEMORY SYSTEMS AND DRUG ADDICTION
- Powerful plasticity processes and associated
memories are formed during drug experiences that
come to dominate behavioural control.
51GDE FACTORS
- These factors could produce an organizational
change in the relationship of these
memory/behavioural systems to one another, and
with other brain systems that could make an
individual more susceptible to drug addiction.
52SCENARIO 1
- Enhanced behavioural control exhibited by one
memory/behavioural system. - Ease of access to common output sites.
- Enhanced plasticity processes.
53Striatum
Hippocampus
Memory Systems Interaction
Amygdala
Addictive
Habit dominance
GDE factors
Behaviour
Nucleus Accumbens
Prefrontal Cortex
Brainstem nuclei
Other Neural Systems
54SCENARIO 2
- Bigger reward signal occurring when drugs of
abuse are administered. - Result in an acceleration of specific types of
learning and memory processes associated with
compulsive drug seeking.
55(No Transcript)
56SCENARIO 3
- Reduction of inhibitory control.
- Could result in alterations in behavioural
control because of a loss of a contribution from
executive systems necessary for appropriate
choice behaviours.
57Striatum
Amygdala
Hippocampus
Memory Systems Interaction
Addictive
Decreased Inhibitory Control
GDE factors
Prefrontal Cortex
Brainstem nuclei
Nucleus Accumbens
Behaviour
Other Neural Systems
58FUTURE WORK
- Need to emphasize the dynamic and interactive
nature of these systems. - Particularly when trying to develop treatment
regimes.
59FUTURE WORK
- The logic behind this claim is that it appears
that certain drugs of addiction modulate
plasticity processes in specific learning and
memory systems but not in others. - While another drug of abuse might have a
different pattern of influences.
60FUTURE WORK
- Certain addictions might be based on certain
neural circuits while addictions to another drug
could be mediated by a different set of neural
circuits. - Examples.