Chapter 16: Autistic Disorder, Stress Disorder and Drug Abuse

1
Chapter 16 Autistic Disorder, Stress Disorder
and Drug Abuse
2
Lecture Outline

• Autistic Disorder
• Stress Disorder
• Physiology of Stress
• PTSD
• Psychoneuroimmunology
• Drug Abuse
• Addiction and Dependence
• Features of Addiction
• Drugs of choice
• Drug Therapy

3
Autism

• Autism impairments of
• Social relations with others
• Ability to communicate
• Imaginative ability
• Incidence of autism is 4/10,000
• Males are 3 times more likely to develop autism

4
Biological Bases of Autism

• Heritability MZ twins exhibit a 96 concordance
  rate for autism
• Autism is associated with neurological disorders
• Phenylketonuria (PKU)
• Tourettes syndrome
• Fragile X syndrome (mental retardation)
• Factors that impair development lead to autism
• Rubella, hydroencephalus
• Drugs such as Thalidomide

5
Stress

• Aversive stimuli can elicit emotional responses
• Behavioral component Fight or Flight response
• Autonomic component Sympathetic activation
• Endocrine secretion of epinephrine, NE
• Physiological reactions to chronic aversive
  stimuli/situations can be damaging
• Stressors the aversive stimuli
• Stress Response our reaction to stressors

6
Hormone Secretion during Stress

• Stressors evoke activity in sympathetic N.S.
• Adrenal glands release
• Epinephrine biases energy flow to muscles,
  increases blood pressure and blood flow to heart
• Norepinephrine increases blood flow and
  pressure
• Glucocorticoids break down protein and fats to
  glucose
• Cortisol secretion is controlled by releasing
  factors from the PVN
• PVN CRF --gt ACTH --gt adrenals secrete
  glucocorticoids
• CRF may act as a stress transmitter

7
Chronic Exposure to Stressors

• Chronic stress is damaging to health
• Air traffic controllers more likely to develop
• High blood pressure
• Ulcers and diabetes
• Chronic secretion of glucocorticoids leads to
• Increased blood pressure (--gt stroke, heart
  attacks)
• Loss of neurons in brain (e.g. hippocampal field
  CA1)
• Suppression of the immune system (--gt illness)
• Suppression of the inflammatory system (delays
  healing)

8
(No Transcript)
9
(No Transcript)
10
Posttraumatic Stress Disorder

• Posttraumatic Stress Disorder (PTSD)
• Acute exposure to intense stressors can have
  delayed effects (Air disasters, war, assault)
• Dreams, recall of trauma event
• Flashback episodes of event
• Intense distress

11
Predisposing Factors for PTSD

• Personality variables that predispose to PTSD
• Tendency to brood about feelings
• Vietnam Veterans study
• Family financial difficulty
• History of drug abuse/dependence
• History of affective disorders
• History of childhood behavior problems
• Genetic factors for PTSD
• Vietnam PTSD soldiers were more likely to possess
  an allele of the dopamine D2 receptor

12
Coping Responses and Stress

• Stress reflects our reaction to stressors
• Coping implies modifying our responses
• Exerting control over aversive stimuli can reduce
  stress responses
• Weiss study rats that avoid shock show fewer
  ulcers
• Coping may involve an increase in the level of
  benzodiazepines in brain (would act via GABA
  sites to reduce anxiety)

13
Psychoneuroimmunology

• Psychoneuroimmunology Study of the interactions
  between the immune system and behavior
• Stress responses can impair the immune system
• Leading to illness and potential death

14
Overview of the Immune System

• Immune system destroys foreign organisms
  (viruses, bacteria, fungi)
• Nonspecific reaction act to destroy organisms or
  infected cells
• Inflammatory reaction damaged cells leak
  substances that increase blood flow
• Phagocytotic white blood cells destroy damaged
  cells
• Cell infection --gt interferon secretion (reduces
  viral replication
• Natural killer cells detect and destroy infected
  cells

15
Immune System Overview, continued

• Specific Immune reactions
• Chemically-mediated immune system produces
  antibodies that recognize the antigens present on
  surface of a foreign cell
• B-lymphocytes produce immunoglobulin antibodies
  that destroy foreign cells
• Cell-mediated antibodies on exterior of
  T-lymphocytes detect foreign antigens (viruses)

16
(No Transcript)
17
Stress and the Immune Response

• Stress increases likelihood of infectious disease
• Students are more likely to be ill during exam
  times
• Death of a spouse leads to illness of survivor
• Explanation stress releases glucocorticoids
  that in turn impair the immune system
• Supporting Evidence
• Bereavement leads to reduced immune response
• Alzheimers caregivers have impaired immune
  response
• Inescapable shock in rats reduces T-cells,
  B-cells and natural killer cells

18
(No Transcript)
19
(No Transcript)
20
Adverse Effects of Drug Abuse

• Alcohol abuse is associated with
• Automobile accidents
• Fetal alcohol syndrome
• Cirrhosis of the liver
• Korsakoffs syndrome
• Cardiac disease
• Risk of intracerebral hemorrhage

21
Addiction and Dependence

• Drug Addiction to sentence
• Physical dependence associated with
• Tolerance decreased drug sensitivity over time
• Withdrawal symptoms opposite of drug effects
• Psychological dependence Drug taking continues
  to ensure pleasurable state

19.5
Carlson - Physiology of Behavior 6/e, Allyn and
Bacon
22
Positive Reinforcement and Drug-Taking

• Drugs activate positive reinforcement mechanisms
  in brain
• Most addictive drugs increase dopamine levels
  within the nucleus accumbens
• Some induce release from presynaptic terminals
• Other drugs block reuptake into presynaptic
  terminal
• Some drugs may act via endogenous opioids
• Immediacy of drug action is crucial to drug
  reinforcement

23
Negative Reinforcement and Drug-Taking

• Behaviors that terminate aversive effects are
  negatively reinforced
• It feels so good when it stops hurting
• Withdrawal symptoms that accompany drug-taking
  are usually aversive
• Starting drug-taking again will terminate the
  withdrawal state
• Drug-taking has positively- and
  negatively-reinforced aspects

19.8
Carlson - Physiology of Behavior 6/e, Allyn and
Bacon
24
Drug Craving

• Craving is an impulsion to reinstate drug-taking
  during abstinence
• Reflects an activation of the mesolimbic dopamine
  system by drug cues (needles, mirrors, pipes,
  etc)
• Unpleasant feelings of abstinence
• Pleasant recall of positive drug state

25
Drug Craving and D3 Receptors

• D3 receptors located within nuc. accumbens may
  mediate drug craving
• D3 receptors are sensitized after cocaine use
• Cocaine-experienced monkeys will self-administer
  the D3 receptor agonist 7-OH-DPAT
• Cocaine-naïve monkeys do not...
• D3 receptor density is increased in nuc accumbens
  of cocaine-overdosed humans

19.11
Carlson - Physiology of Behavior 6/e, Allyn and
Bacon
26
Cocaine

• Cocaine is a potent DA agonist
• Binds and inactivates the DA transporter
• Blocks reuptake to increase DA in synapse
• Cocaine reinforcement is assessed using
• Self-administration paradigm animal presses
  lever that results in cocaine infusion via
  jugular catheter
• Conditioned Place Preference paradigm Does the
  animal prefer a compartment previously paired
  with the drug cue?

27
Cocaine Reinforcement The Role of the Nucleus
Accumbens

• Positive Reinforcement and Cocaine
• Cocaine increases synaptic DA within the
  accumbens
• Animals will self-inject DA agonists directly
  into the nuc. Accumbens (NAC)
• Lesions of the NAC impairs self-administration of
  cocaine in rats
• Negative Reinforcement and Cocaine
• Cocaine withdrawal results in reduced NAC dopamine

28
(No Transcript)
29
(No Transcript)
30
Alcohol

• Alcohol effects depend on dose
• Low doses reduces anxiety
• Med-High doses sedation and incoordination
• Alcohol consumption produces
• Positive reinforcement mild euphoria
• Negative reinforcement The aversive state of
  anxiety is reduced by alcohol consumption

31
Neural Bases of Alcohol Actions

• Alcohol increases DA levels within NAC
• Alcohol has effects at two receptor sites
• Inverse agonist at NMDA sites
• Mediates increased DA release after alcohol
• Mediates the sedative and anxiolytic effects of
  alcohol
• Indirect agonist at GABAA sites
• Mediates the anxiolytic effect of alcohol

32
(No Transcript)
33
Heritability of Alcohol Abuse

• Twin studies MZ twins show greater concordance
  for alcoholism than DZ twins
• Cross-Fostering studies examine rates of
  alcoholism in children adopted while young
• Environment (one or more ALC adopted parents)
• Heritage (one or more ALC biological parents)
• Male steady drinking is strongly influenced by
  heritage
• Male/female binge drinking is an interaction
  effect

34
Therapies for Drug Dependence

• Cocaine use is reduced by
• Blockade of dopamine receptors
• Issue this also produces dysphoria and anhedonia
• Blockade of D3 receptors
• Use of cocaine immunization
• Alcohol intake is reduced by
• 5-HT reuptake blockers
• Opiate antagonists (naltrexone)