COGNITIVE SCIENCE 17 Drug Abuse or … Drug Abuse or… For Big Kids

1
COGNITIVESCIENCE17Drug Abuse or Drug Abuse
orFor Big Kids
Mike Datko, B.S.
2
Features of drug abuse and addiction

• Definition how are abuse and addiction defined
  clinically?
• Positive reinforcement
• Negative reinforcement
• Opponent process theory
• Craving and relapse

3
Clinical definitions

• Drug abuse is defined by the Diagnostic and
  Statistical Manual of Mental Disorders
• A. A maladaptive pattern of substance use
  leading to clinically significant impairment or
  distress, as manifested by one (or more) of the
  following, occurring within a 12-month period
• 1. Recurrent substance use resulting
  in a failure to fulfill major role obligations at
  work, school, or home (e.g., repeated absences or
  poor work performance related to substance use
  substance-related absences, suspensions or
  expulsions from school neglect of children or
  household)
• 2. Recurrent substance use in
  situations in which it is physically hazardous
  (e.g., driving an automobile or operating a
  machine when impaired by substance use)
• 3. Recurrent substance-related legal
  problems (e.g., arrests for substance-related
  disorderly conduct)
• 4. Continued substance use despite
  having persistent or recurrent social or
  interpersonal problems caused or exacerbated by
  the effects of the substance (e.g., arguments
  with spouse about consequences of intoxication,
  physical fights)
• B. The symptoms have never met the
  criteria for Substance Dependence for this class
  of substance.

A state of drug dependence is defined similarly,
with the additional requirement of the
manifestation of physical withdrawal symptoms
when drug use is stopped.
Koob (at UCSD) described addiction as involving
a cycle of spiraling dysregulation of brain
reward systems that progressively increases,
resulting in the compulsive use and loss of
control over drug taking.
4
Positive reinforcement

• An increase in the future frequency of a behavior
  due to the addition of a stimulus immediately
  following a response. (from Wikipedia)
• If a person has a positive experience as a result
  of taking a drug, and subsequently takes more of
  the drug in the future, it is called positive
  reinforcement.

5
Negative Reinforcement

• Relief from withdrawal symptoms
• If no withdrawal symptoms are present, relief
  from stress caused by emotional or life
  circumstances (or more generally, compensating
  for or reversing some physiological)
• Example Someone who drinks alcohol or takes
  other anxiolytic (anxiety-relieving) drugs to
  relieve naturally occurring anxiety is
  experiencing negative reinforcement.

6
Opponent-process theory

• Initially, positive effects of a drug easily
  outweigh negative effects.
• Net effect of taking a drug is very positive.

• As usage continues, homeostatic mechanisms
  become better at counteracting the acute effects
  of the drug.
• Net effect is still positive, but less and less
  so.

• At this point, positive effects of drug are
  equal to bodys homeostatic response.
• Net effect is neutral (must have drug to feel
  normal).

• In late stages of addiction, homeostatic set
  point has changed (a phenomenon called
  allostasis).
• Net effect of drug use is negative, and the user
  must have the drug in order to prevent very
  negative feelings.

Diagrams from Neurotopia.com
7

• Addictive potential of a drug is related to its
  chemical properties as well as its route of
  administration.
• Route of administration affects how quickly drug
  enters bloodstream.
• - Some routes, from fastest to slowest
• Intravenous injection, smoking, nasal
  insufflation, drinking/eating
• Chemical properties of drug affect how
  easily/quickly it crosses the Blood Brain Barrier
  once its in the bloodstream.

Amphetamine
Methamphetamine
8
Craving and Relapse

• Incentive salience Stimuli associated with drug
  taking become exciting and motivating they
  become a provocation to act (from your book, pg.
  618).
• Craving is triggered in people with a history of
  drug abuse after exposure to drug-related stimuli
  (pictures, paraphernalia, smells, locations,
  people)
• Brain areas involved in craving
• Medial Prefrontal Cortex and Nucleus Accumbens
• In users, these areas show greater responses to
  drug-related cues than in non-users, but are less
  active at rest in users than in non users.

9
Common Drugs of Abuse and their Effects

• Opiates
• Stimulants
• Cocaine
• Methamphetamine
• Nicotine
• Alcohol
• Cannabis
• http//learn.genetics.utah.edu/content/addiction/d
  rugs/mouse.html

10
Opiates

• Primarily heroin and oxycodone (most addictive)
• Also, morphine, hydrocodone (Vicodin),
  methylmorphine (codeine)
• Acute positive effects euphoria, relaxation,
  analgesia (pain relief)
• Acute negative effects constipation, depressed
  breathing and heart rate (overdose can result in
  death because of this).

11

• Opiates site/mechanism of action
• Mu and delta opiate receptor agonist.
• Mimics the effects of the bodys naturally
  occurring endorphins (but much stronger effect
  because concentrations are usually higher than
  those of endorphins)
• Activation of opiate receptor inhibits release of
  GABA from an interneuron
• Inhibits the inhibition (from GABA) on a
  neighboring neuron, which then releases more
  dopamine than usual to a post-synaptic neuron.
  (detailed diagram on next slide).
• Studies with KO mice that lack mu-opiate receptor
• KO mice do not develop conditioned
  place-preference or certain withdrawal symptoms.
  

12
(No Transcript)
13
Stimulants Cocaine and Methamphetamine

• Sites of action
• Cocaine inhibits dopamine reuptake in the
  synapse dopamine sits in synapse for longer
  time and at higher concentrations.
• Methamphetamine (and regular amphetamine) Causes
  vesicles containing dopamine to rupture within
  the presynaptic neuron and reverses the action of
  dopamine reuptake channels.

14
Stimulants effects of abuse

• Figure 18.10 in book (pg 627) after 25 days,
  close to 100 fatality rate in rats allowed to
  freely administer cocaine (vs 40 fatality rate
  for heroin).
• Chronic users often develop hallucinations,
  delusions of persecution, mood disturbances, and
  repetitive behaviors which strikingly resemble
  symptoms of schizophrenia (role of dopamine
  system?).
• Figure 18.12 (pg 628) significantly lower
  concentrations of dopamine transporters, as
  measure with PET, in meth abusers compared to
  controls.
• one issue with this type of study is the
  ambiguity of the cause of reduced dopamine
  transporters/dopaminergic terminals did meth
  abuse cause this difference or was it the result
  of previously existing factors such as genetics
  (in which case, did these genetic differences
  predispose the individual to drug abuse?)?
• Figure 18.14 (pg 629) significantly lower
  dopamine receptors in striatum of meth abusers.
• Damaged dopamine system higher risk of
  developing Parkinsons Disease as age increases?

15
Nicotine

• Mechanism of action
• Agonist at nicotinic acetylcholine receptors.
• Ionotropic receptor (rapid effects of activation)
• Most nicotinic receptors are heteroreceptors on
  postsynaptic neurons (their activation causes the
  release of other neurotransmitters into the
  synaptic cleft).
• Nicotine is responsible for addiction and craving
  associated with cigarettes, but is not the major
  cause of health problems.
• Other ingredients and carcinogens found in smoke
  lead to cancer and cardiovascular problems.
• Nicotine alone is only toxic in high doses

16
Alcohol

• Mechanism/site of action
• Indirect agonist at GABA-A receptors and indirect
  antagonist at NMDA receptors.
• Produces both positive and negative
  reinforcement
• Mild euphoria, rise in dopamine in NAC positive
  reinforcement
• Reduction of anxiety (GABA actions) negative
  reinforcement

17

• Unlike with most drugs, severe withdrawal
  symptoms from alcohol can be fatal.
• Convulsions and seizures result from a
  hypersensitization of NMDA receptors that occurs
  with long-term alcohol use.
• Long-term use leads to lower amounts of dopamine
  receptors in the striatum.
• Korsakoffs syndrome anterograde and retrograde
  amnesia, apathy, and other symptoms
• Result of thiamine deficiency that often occurs
  as a result of alcoholism

18
Cannabis

• Main psychoactive compound is Tetrahydrocannabinol
  (THC)
• Mechanism/site of action agonist at CB1
  receptors.
• CB1 receptors are normally sensitive to
  endogenous cannabanoids like anandamide.
• Like other drugs of abuse, use leads to temporary
  increase in dopaminergic activity in key areas
• Hippocampus contains a large concentration of CB1
  receptors
• May explain effect of cannabis on memory
  formation
• One of the few drugs of abuse that has extremely
  low overdose potential.
• Very low concentrations of CB1 receptors in brain
  stem

19
Treatments and Therapies

• Opiates
• Methadone mu-opiate receptor agonist
• Has effects similar to heroin but administered in
  a controlled setting (clinic, by nurses/doctors)
  and taken in liquid form.
• Buprenorphine mu-opiate partial agonist
• Competes at same receptor as normal opiates but
  produces much less of an effect when it binds.

20
Treatments stimulants

• Immunotherapy
• Create and administer proteins that make the
  immune system attack a given drug.
• For example, giving someone a dose of proteins
  that resemble cocaine but are not actually
  cocaine will train their immune system to
  eliminate actual cocaine as if it were a
  disease-inducing virus.
• Gamma-vinyl GABA (GVG) GABA receptor agonist
  that reduces the reinforcing effects of cocaine.

21
Treatments Nicotine

• Nicotine gum and patch
• Maintains a constant level of nicotine to avoid
  withdrawal symptoms, but does not produce a
  nicotine buzz because it takes much longer to
  enter the bloodstream than smoked nicotine.
• Bupropion (Wellbutrin, Zyban) Catecholamine
  reuptake inhibitor that reduces cravings.

22
Treatments Alcohol

• Ro15-4513 prevents intoxication by blocking
  alcohol binding site on GABA-A receptor.
• NOT used because it would enable people to
  potentially drink toxic amounts of alcohol
  without feeling any noticeable effects.
• Naltrexone opiate receptor antagonist
• Alcohol induces the release of endogenous opioids
  (endorphins).
• Davidson, Swift, and Fitz (1996) study with
  social drinkers found that subjects who were
  taking naltrexone prior to a drinking session
  drank slower and drank less than controls.
• Acamprosate NMDA receptor antagonist
• Eases withdrawal symptoms and makes alcoholics
  less likely to drink again after treatment.

23
Other facts/info

• The majority of people who try addictive drugs do
  not become addicted.
• Heredity (genetics) seems to dictate who becomes
  addicted after trying a drug, but environment
  (friends, family, etc.) is a more important
  factor in determining whether or not someone will
  try a drug initially.