The%20Synapse,%20Substance%20Abuse,%20and%20Addiction

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The Synapse, Substance Abuse, and Addiction

• Module 2.1 The Concept of the Synapse

• Module 2.2 Chemical Events at the Synapse

• Module 14.1Substance Abuse and Addiction

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Synaptic Transmission OverviewLink to Animated
Video

• Http//www.sumanasinc.com/webcontent/animations/co
  ntent/synaptictransmission.html

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The Concept of the Synapse

• Synapse gap between one neurons presynaptic
  terminal and another receiving neuron
• Discovered by Santiago Ramon y Cajal in the late
  1800s

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The Concept of the Synapse

• In 1906, Charles Scott Sherrington
• coined the term synapse and proposed that neurons
  communicate by transmitting chemicals at synapses
• conducted research on synaptic communication by
  studying reflexes (automatic muscular responses
  to stimuli).

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Reflex arc the complete circuit from sensory
neuron to muscle response
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Sherrington deduced three properties of reflexes

1. Reflexes are slower than conduction along a
   single axon.

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Sherrington deduced three properties of reflexes

• 2. Several weak stimuli presented at slightly
  different times or slightly different locations
  produces a stronger reflex than a single stimulus
  does.

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Sherrington deduced three properties of reflexes

• 3. As one set of muscles relaxes, another set
  becomes excited.

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John Eccles (1964)

• Postsynaptic neuron receives the message
• Presynaptic neuron delivers the synaptic
  potential

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• Spatial summation synaptic input from several
  locations can have a cumulative effect and
  trigger a nerve impulse
• Temporal summation repeated stimuli can have a
  cumulative effect and can produce a nerve impulse
  when a single stimuli is too weak.
• Link to animation
• of Summation
• of Postsynaptic
• Potentials

• http//sites.sinauer.com/neuroscience5e/animations
  05.02.html

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Graded potentials

• either depolarize (excite) or hyperpolarize
  (inhibit) the postsynaptic neuron
• decay over time and space

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The Concept of the Synapse

• Excitatory postsynaptic potential (EPSP)
  depolarizes neurons membrane
• is a graded (excitatory) potential that decays
  over time and space.
• The cumulative effect of EPSPs are the basis for
  temporal and spatial summation.
• Inhibitory postsynaptic potential (IPSP)
  hyperpolarizes membrane.
• Serves as an active brake, that suppresses
  excitation.

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The Concept of the Synapse

• The spontaneous firing rate refers to the
  periodic production of action potentials despite
  synaptic input.
• EPSPs increase the nerve cells spontaneous
  firing rate.
• IPSPs decrease the nerve cells spontaneous
  firing rate.

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Chemical Events at the Synapse

• Otto Loewi (1920) Discovered that transmission
  of a message across the synapse occurs by
  chemical means.

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Neuroanatomy Handout 2 The Synapse and
Neurotransmitters

• Synaptic cleft (E)
• Axon membrane (A)
• Presynaptic membrane (A1)
• Synaptic vesicles (B) tiny spherical packets
  located in the presynaptic terminal where
  neurotransmitters are held for release
• Neurotransmitters (C) chemicals that travel
  across the synapse and allow communication
  between neurons
• Neurotransmitter fragments (C1)

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Neurotransmitters

• Approx. 100 different kinds
• Neurons synthesize neurotransmitters and other
  chemicals from substances provided by the diet.
• Acetylcholine is synthesized from choline found
  in milk, eggs, and nuts.
• Serotonin is synthesized from tryptophan found in
  turkey and soy.

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Major sequence of events for neurotransmitters

1. The neuron synthesizes chemicals that serve as
   neurotransmitters.
2. Neurons store neurotransmitters in axon terminals
   or transport them there (transportation from cell
   body can take hours or days).
3. An action potential triggers the release of
   neurotransmitters into the synaptic cleft.

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Major sequence of events for neurotransmitters

• Exocytosis (D) refers to the excretion of the
  neurotransmitter from the presynaptic terminal
  into the synaptic cleft.
• Triggered by an action potential arriving from
  the axon.

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Major sequence of events for neurotransmitters

1. The neurotransmitters travel across the cleft and
   attach to the postsynaptic membrane (F) at the
   postsynaptic receptor sites (G).
2. The neurotransmitters separate from the
   receptors.
3. The neurotransmitters are taken back into the
   presynaptic neuron, diffuse away, or are
   inactivated by chemicals.

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Major sequence of events for neurotransmitters

• Reuptake (endocytosis) (H) refers to the
  presynaptic neuron taking up most of the
  neurotransmitter molecules intact and reusing
  them.

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Chemical Events at the Synapse

• A hormone is a chemical secreted by a gland or
  other cells that is transported to other organs
  by the blood where it alters activity.
• Endocrine glands are responsible for the
  production of hormones.
• Hormones are important for triggering
  long-lasting changes in multiple parts of the
  body.

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Pituitary Gland

• Attached to the hypothalamus and consisting of
  two distinct glands that each release a different
  set of hormones
• Anterior pituitary- composed of glandular tissue
  and synthesizes six hormones.
• Posterior pituitary- composed of neural tissue
  and can be considered an extension of the
  hypothalamus

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Drugs and the Synapse

• Drugs work by doing one or more of the following
  to neurotransmitters
• Increasing the synthesis.
• Causing vesicles to leak.
• Increasing release.
• Decreasing reuptake.
• Blocking the breakdown into inactive chemical.
• Directly stimulating or blocking postsynaptic
  receptors.

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Link to Mouse Party
http//learn.genetics.utah.edu/content/addiction/m
ouse/
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Drugs and the Synapse

• Drugs either facilitate or inhibit activity at
  the synapse.
• Antagonistic drugs block the effects of
  neurotransmitters.
• Agonist drugs mimic or increase the effects of
  neurotransmitters.

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Drugs and the Synapse

• A drug has an affinity for a particular type of
  receptor if it binds to that receptor.
• Can vary from strong to weak.
• The efficacy of the drug is its tendency to
  activate the receptor.
• Drugs can have a high affinity but low efficacy.

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Drugs and the Synapse

• Almost all abused drugs stimulate dopamine
  release in the nucleus accumbens,
• small subcortical area rich in dopamine receptors
• an area responsible for feelings of pleasure

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Drugs and the Synapse

• Drugs are categorized according to their
  predominant action or effect upon behavior
• Stimulant drugs increase excitement, alertness,
  motor activity and elevate mood.
• Examples amphetamines, cocaine, methylphenidate
  (Ritalin), MDMA (Ecstasy), nicotine
• Stimulant drugs directly stimulate dopamine
  receptor types D2, D3, and D4.

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Drugs and the Synapse

• Amphetamines stimulate dopamine synapses by
  increasing the release of dopamine from the
  presynaptic terminal.
• Cocaine blocks the reuptake of dopamine,
  norepinephrine, and serotonin.
• Methylphenidate (Ritalin) also blocks the
  reuptake of dopamine but in a more gradual and
  more controlled rate.
• Often prescribed for people with ADD

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Drugs and the Synapse

• MDMA (Ecstasy)
• increases the release of dopamine at low doses
  that account for its stimulant properties
• increases the release of serotonin at higher
  doses accounting for its hallucinogenic
  properties.
• Research indicates ecstasy use may contribute to
  higher incidences of anxiety and depression as
  well as memory loss and other cognitive deficits.

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Drugs and the Synapse

• Nicotine
• active ingredient in tobacco
• stimulates an acetylcholine receptor known as the
  nicotinic receptor, found in
• central nervous system
• nerve-muscle junction of skeletal muscles
• nucleus accumbens

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Drugs and the Synapse

• Opiate drugs
• derived from opium poppy
• decrease sensitivity to pain and increase
  relaxation
• Examples morphine, heroin, methadone.

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Drugs and the Synapse

• Endorphins
• naturally produced neurotransmitters
• ease pain
• inhibit GABA, allowing dopamine to exert its
  effect
• attach to the same receptors to which opiates
  attach.

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Drugs and the Synapse

• Tetrahydocannabinol (THC)
• active ingredient in marijuana
• attaches to cannabinoid receptors, especially in
  the cerebral cortex, cerebellum, basal ganglia,
  and hippocampus.
• Cannabinoids chemicals related to THC, typically
  used medically
• Anandamide and 2-AG are the endogenous chemicals
  that attach to these receptors.

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Drugs and the Synapse

• Hallucinogenic drugs
• cause distorted perception
• may resemble serotonin in their molecular shape
• stimulate serotonin type 2A receptors (5-HT2A) at
  inappropriate times or for longer duration than
  usual thus causing their subjective effect.

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Alcohol and Alcoholism

• Alcohol
• is associated with relaxation
• in greater amounts impairs judgment and damages
  the liver and other organs
• dependence (alcoholism) is the habitual use of
  alcohol despite medical or social harm

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Alcohol and Alcoholism

• Alcohol has a number of diverse physiological
  effects, including
• Enhanced response by the GABAA receptor
• Blockage of glutamate receptors
• Increased dopamine activity

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Alcohol and Alcoholism

• Strong influence of genetics on alcoholism
• The genetic basis for early-onset alcoholism is
  stronger than for later-onset, especially in men
• Researchers distinguish between two types of
  alcoholism
• Type I/Type A
• Type II/Type B

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Alcohol and Alcoholism

• Type I/Type A characteristics include
• Later onset (usually after 25)
• Gradual onset
• Fewer genetic relatives with alcoholism
• Equal quantity between men and women

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Alcohol and Alcoholism

• Type II/Type B characteristics include
• Earlier onset (usually before 25)
• More rapid onset
• More genetic relatives with alcoholism
• Men outnumber women

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Alcohol and Alcoholism

• Genes influence the likelihood of alcoholism in
  many ways, such as
• being more sensitive and needing more alcohol to
  provide reinforcement
• being linked with impulsivity
• influencing responses to stress and
  anxiety-inducing experiences
• likelihood of prenatal exposure to alcohol

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Alcohol and Alcoholism

• Research on sons of alcoholic fathers shows
• Less average intoxication after one drink
• Stress decreases more than for the average person
• Smaller than normal amygdala

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Addiction

• Various factors contribute to continued substance
  abuse
• Tolerance The bodys decrease in response to a
  drug with repeated use
• Withdrawal Uncomfortable/painful symptoms once
  drug use is discontinued
• Cravings develop in response to cues
• Brain reorganization (nucleus accumbens and
  prefrontal cortex)

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Medications to Combat Alcohol Abuse

• Revia (naloxone) blocks opiate receptors, thereby
  decreasing the pleasure from alcohol.
• Antabuse (disulfiram) works by making user sick
  (only moderately effective)
• ?

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Medications to Combat Opiate Abuse

• Methadone is an opiate similar to heroin and
  morphine but is absorbed and metabolized slowly
• Perceived to be less harmful than other drugs
• Assumed to satisfy cravings associated with
  previous drug use
• Levomethadyl acetate (LAAM) is similar to
  morphine but can be taken three times a week
  rather than daily