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DRUG ADDICTION AND REWARD

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NEXT TO CAFFEINE, TOBACCO IS THE MOST WIDELY ABUSED DRUG IN OUR SOCIETY. ... SMOKER'S SYNDROME--CHEST PAIN, LABORED BREATHING, WHEEZING, COUGHING, INCREASED ... – PowerPoint PPT presentation

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Title: DRUG ADDICTION AND REWARD


1
DRUG 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.

2
FIVE 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.

3
TOBACCO
  • CONSIDERABLE TOLERANCE DEVELOPS TO SOME OF THE
    IMMEDIATE ADVERSE EFFECTS OF TOBACCO.
  • -NON-SMOKER.
  • -SMOKER.

4
TOBACCO
  • HEAVY SMOKERS WHO STOP SMOKING CAN EXPERIENCE
  • DEPRESSION, ANXIETY, RESTLESSNESS, IRRITABILITY,
    CONSTIPATION, DIFFICULTIES IN SLEEPING AND
    CONCENTRATION.

5
LONG-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.

6
LONG-TERM TOBACCO USE
  • OTHER CANCERS--MOUTH, THROAT, KIDNEYS, PANCREAS,
    BLADDER AND STOMACH.
  • CARDIOVASCULAR DISEASE--CULMINATING IN HEART
    ATTACK OR STROKE.

7
ALCOHOL
  • APROXIMATELY 2/3 OF THE POPULATION CONSUME
    ALCOHOLIC BEVERAGES.
  • OF THESE, 15 MILLION ARE ADDICTED.

8
ALCOHOL
  • MODERATE DOSES--COGNITIVE, PERCEPTUAL, VERBAL AND
    MOTOR IMPAIRMENT.
  • CAN ALSO LEAD TO INTERESTING BEHAVIORS IN SOCIAL
    SITUATIONS.

9
ALCOHOL
  • HIGH DOSES--UNCONCIOUSNESS AND RISK OF DEATH FROM
    RESPIRATORY DEPRESSION.

10
ALCOHOL 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.

11
ALCOHOL WITHDRAWAL
  • 15-30 HOURS.
  • -CONVULSIVE ACTIVITY.

12
ALCOHOL WITHDRAWAL
  • 2-3 DAYS.
  • DELERIUM TREMENS (DTs).
  • DISTURBING HALLUCINATIONS, DELUSIONS, AGITATION,
    CONFUSION, HYPERTHERMIA AND RAPID HEARTBEAT.

13
CHRONIC ALCOHOL CONSUMPTION
  • EXTENSIVE BRAIN DAMAGE.
  • CIRRHOSIS OF THE LIVER.
  • HEART DAMAGE.
  • GI TRACT DAMAGE.
  • TRAFFIC FATALITIES.

14
ALCOHOL AND DEVELOPMENT
  • LIKE NICOTINE, ALCOHOL READILY PENETRATES THE
    PLACENTAL MEMBRANE AND AFFECTS THE FETUS.
  • FETAL ALCOHOL SYNDROME (FAS).

15
ALCOHOL HAS MULTIPLE SITES OF ACTION
  • CALCIUM CHANNELS.
  • GABA RECEPTORS.
  • GLUTAMATE RECEPTORS.
  • 2ND MESSENGER SYSTEMS.

16
MARIJUANA
  • THE PSYCHOACTIVE EFFECTS OF MARIJUANA ARE LARGELY
    ATTRIBUTABLE TO A CONSTITUENT CALLED THC
    (DELTA-9-TETRAHYDROCANNABINOL).

17
HAZARDS
  • LUNG DAMAGE.
  • MORE LIKELY TO DEVELOP CHRONIC BRONCHITIS AND
    ASTHMA.

18
MECHANISM OF ACTION
  • THC BINDS TO RECEPTORS THAT ARE DENSE IN THE
    BASAL GANGLIA, HIPPOCAMPUS, CEREBELLUM AND
    NEOCORTEX.

19
POT AND THE BRAIN
20
ENDOGENOUS LIGAND?
  • RECENTLY, THE GENE FOR THE THC RECEPTOR HAS BEEN
    CLONED.
  • TRIGGERED RESEARCH FOR AN ENDOGENOUS THC-LIKE
    CHEMICAL.
  • ANANDAMIDE.

21
COCAINE
  • COCAINE HYDROCHLORIDE.
  • USERS REPORT BEING SWEPT AWAY BY A WAVE OF
    WELL-BEING.
  • CONFIDENT, ALERT, ENERGETIC, FRIENDLY, OUTGOING,
    FIDGETY, TALKATIVE.

22
HAZARDS
  • RISK OF SEIZURES, LOSS OF CONCIOUSNESS, DEATH
    FROM RESPIRATORY ARREST OR STROKE.
  • INSOMNIA, TREMORS, NAUSEA AND PSYCHOTIC BEHAVIOR.

23
MECHANISM OF ACTION
  • EXERTS BEHAVIORAL EFFECT BY FACILITATING
    CATECHOLAMINERGIC TRANSMISSION.
  • HOW?

24
OPIATES
  • EXTRACTED FROM SAP OF SEEDS FROM THE OPIUM POPPY.
  • MORPHINE AND CODEINE.

25
OPIATES
  • HEROIN IS A SYNTHESIZED OPIATE.
  • ADDITION OF 2 ACETYL GROUPS TO THE MORPHINE
    MOLECULE.

26
OPIATES
  • THE EFFECT OF OPIATES MOST VALUED BY OPIATE
    ADDICTS IS THE RUSH THAT FOLLOWS IV INJECTION.
  • OPIATES ARE HIGHLY ADDICTIVE.

27
COLD TURKEY?
  • SYMPTOMS OF OPIATE WITHDRAWAL HAVE BEEN GREATLY
    EXAGGERATED.
  • MAIN RISKS OF OPIATE ADDICTION ARE INDIRECT.

28
MECHANISM OF ACTION
  • BIND TO OPIATE RECEPTORS.
  • ENDOGENOUS LIGAND?
  • ENDORPHINS.

29
BIOPSYCHOLOGICAL THEORIES OF ADDICTION
  • PHYSICAL-DEPENDENCE THEORY
  • POSITIVE-INCENTIVE THEORY
  • -PRIMARY REASON MOST ADDICTS TAKE DRUGS IS TO
    OBTAIN THE PLEASURABLE EFFECTS OF THE DRUG.

30
ROBINSON 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.

31
REWARD CIRCUITS IN THE BRAIN
  • OLDS AND MILNER (1954)
  • INTRACRANIAL SELF-STIMULATION.

32
ICSS
  • 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.

33
ICSS
34
OLDS 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).

35
REWARD 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.

36
REWARD 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.

37
THE 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.

38
NEUROANATOMICAL NOTE
  • SUBSTANTIA NIGRA--gtSTRIATUM (NIGROSTRIATAL
    SYSTEM).
  • VTA--gtLIMBIC AND CORTICAL STRUCTURES
    (MESOCORTICAL SYSTEM).
  • VTA--gtNUCLEUS ACCUMBENS.

39
EVIDENCE
  • MAPPING STUDIES MANY OF THE BRAIN SITES AT WHICH
    ICSS OCCURS ARE PART OF THE DOPAMINE SYSTEM.
  • CEREBRAL DIALYSIS STUDIES MICRODIALYSIS.

40
EVIDENCE
  • 3) DOPAMINE AGONIST AND ANTAGONIST STUDIES
  • 4) LESION STUDIES

41
NEURAL 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).

42
SELF-ADMINISTRATION
43
CPP
44
DOPAMINE AND ADDICTION
  • LAB ANIMALS SELF-ADMINISTER MICROINJECTIONS OF
    ADDICTIVE DRUGS DIRECTLY INTO BRAIN AREAS
    INNERVATED BY THE DOPAMINE SYSTEM BUT NOT OTHER
    BRAIN AREAS.

45
DOPAMINE AND ADDICTION
  • INTRACRANIAL INJECTIONS INTO SIMILAR BRAIN AREAS
    PRODUCE CPPS.
  • ADDICTIVE DRUGS INCREASE REWARDING EFFECTS OF
    ELECTRICAL STIMULATION.

46
DOPAMINE AND ADDICTION
  • DISRUPTION OF DOPAMINE SYSTEM WITH SELECTIVE
    LESIONS OR ANTAGONISTS REDUCE THE REWARDING
    EFFECTS OF ADDICTIVE DRUGS.

47
DOPAMINE 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.

48
MULTIPLE 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.

49
MULTIPLE 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.

50
MULTIPLE MEMORY SYSTEMS AND DRUG ADDICTION
  • Powerful plasticity processes and associated
    memories are formed during drug experiences that
    come to dominate behavioural control.

51
GDE 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.

52
SCENARIO 1
  • Enhanced behavioural control exhibited by one
    memory/behavioural system.
  • Ease of access to common output sites.
  • Enhanced plasticity processes.

53
Striatum
Hippocampus
Memory Systems Interaction
Amygdala
Addictive
Habit dominance
GDE factors
Behaviour
Nucleus Accumbens
Prefrontal Cortex
Brainstem nuclei
Other Neural Systems
54
SCENARIO 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
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56
SCENARIO 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.

57
Striatum
Amygdala
Hippocampus
Memory Systems Interaction
Addictive
Decreased Inhibitory Control
GDE factors
Prefrontal Cortex
Brainstem nuclei
Nucleus Accumbens
Behaviour
Other Neural Systems
58
FUTURE WORK
  • Need to emphasize the dynamic and interactive
    nature of these systems.
  • Particularly when trying to develop treatment
    regimes.

59
FUTURE 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.

60
FUTURE 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.
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