Psychopharmacology - PowerPoint PPT Presentation

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Psychopharmacology

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Pre-synaptic receptors Post-synaptic receptors - - precursors NT x 1. produce 2. pack 3. release 4. Bind 5. Post-synaptic changes (e.g., epsp) + + AP Ca++ inflow – PowerPoint PPT presentation

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Title: Psychopharmacology


1
Neurotransmitters
precursors
1. produce
AP ? Ca inflow
Pre-synaptic Neuron (axon)
Post-synaptic neuron (dendrite)
synaptic cleft
2
Pharmacology
  • A drug can do only two things, either
  • Increase the effect of neurotransmitter X
    (agonist)
  • Decrease the effect of neurotransmitter X
    (antagonist)
  • Thus, in order to understand the action of a
    drug Y, we need to understand the neurochemical
    system it interacts with.
  • In other words, we need to understand how
    Neurotransmitter X
  • - is produced released from the
    pre-synaptic neuron
  • acts on the receptors of the post-synaptic neuron
  • is removed from the synaptic cleft

3
Specific Neurotransmitter Systems ( drugs that
affect them)
  • Acetylcholine
  • Monoamines
  • Dopamine
  • Noradrenaline Adrenaline
  • Serotonin
  • Amino Acids
  • Glutamate
  • GABA
  • Opioids
  • THC
  • Adenosine (caffeine)

4
  • Receptors for Acetylcholine
  • Muscarinic
  • Nicotinic

Cholinergic neurons (release Acetylcholine)
1. produce
Pre-synaptic Neuron (axon)
Post-synaptic neuron (dendrite)
5
Belladonna (atropine)
curare
6
Acetylcholine (Ach)
  • Important for
  • Muscle Botox prevents release by terminal
    buttons (Antagonist)
  • Vigilance Nicotine mimics Ach effect in brain
    (Agonist)
  • Memory Anti-cholinesterase drugs for
    Alzheimers disease (Agonist)
  • Learning Anticholinergic drugs (to prevent
    vomit) (Antagonist)
  • Autonomic Nervous System
  • Cholinergic neurons (release Ach)
  • Receptors
  • Nicotinic (ionotropic) stimulated by nicotine,
    blocked by curare
  • Muscarinic (metabotropic) blocked by atropine
    (belladona)

7
  • Receptors for dopamine
  • D1, D2, D4

Dopaminergic neurons (release dopamine)
Inactive substance
D2
L-Dopa
dopamine
Precursor
D2

Post-synaptic changes
Bind
D1
Cocaine, amphetamine, Methylphenidate
(ritalin) Makes dopamine transporter work in
reverse
Pre-synaptic Neuron (axon)
Post-synaptic neuron (dendrite)
8
Dopamine (DA)
  • Important in
  • Movement control death of dopaminergic cells
    in Parkinsons disease
  • Drug addiction amphetamine, cocaine
    (agonist)
  • Schizophrenia (?) anti-psychotic drugs
    (antagonists)
  • ADHD metylphenidate (ritalin)
  • dopaminergic neurons (release DA)
  • Substantia nigra movement control
  • Ventral Tegmental Area (VTA) drug addiction
  • VTA to frontal cortex schizophrenia (?)
  • Receptors D1, D2, D4
  • Group Activity
  • Would PD treatment with L-dopa increase or
    decrease hallucinations? (one of the symptoms of
    schizophrenia)
  • Would antipsychotic drugs produce PD like
    symptoms as a side effect (e.g., motor problems)?
    Why? Why not?
  • Schizophrenic patients often fail to take their
    medication, despite the benefitial effects. Can
    you provide a physiological explanation? (hint
    which systems does the drug block?)

9
TheReward System
Dopamine
Dopamine
  • Activities of survival (sex, feed) activate the
    reward system

Drugs of abuse similarly activate the reward
system

Electrical stimulation of the reward system is
also addictive
10
Dopamine release in the nucleus accumbens
11
Cocaine and Amphetamine administration
distribution
  • Administration
  • intranasal
  • intravenous
  • smoke (crack)
  • Distribution
  • Crack is more liposoluble, thus stronger
    effect!
  • Cocaine has a very short half life (40 mins)

12
Overview- neurotransmitters
  • Acetylcholine
  • Dopamine
  • Adrenaline
  • Serotonine
  • Glutamate
  • GABA
  • Opioids
  • THC (cannabis)

13
Noradrenaline Adrenaline
  • Aka norepinephrine epinephrine
  • Important for
  • Vigilance (adrenaline response)
  • Noradrenaline acts as a neurotransmitter
  • Adrenaline acts also as a hormone
  • Receptors
  • Alpha
  • Beta beta-blockers are used for hypertension

14
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15
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16
Serotonin (5-HT)
  • Important in
  • Depression
  • Receptors
  • Way too many!
  • Drugs
  • Fluoxetine (prozac) inhibitor of reuptake
    (recycle) (SSRI)
  • LSD agonist of 5-HT2A
  • Ectasy agonist for serotonin and agonist for
    noradrenaline

17
Glutamate
  • Is the most pervasive excitatory NT in the brain
  • Receptors
  • Four types (remember NMDA)
  • Important in
  • Learning (NMDA receptor in the hippocampus)
  • Drugs
  • Alcohol NMDA antagonist
  • Sleepy, impaired cognitive performance
  • Alcohol withdrawal ? seizures

18
GABA
  • Is the most pervasive inhibitory NT in the brain
  • Receptors
  • GABAa opens Cl- channel
  • GABAb opens K
  • Question does it puzzle you that, being GABA an
    inhibitory NT, GABAa and GABAb receptors open
    channels of different polarity? Justify
  • Drugs
  • Benzodiazepines (valium) GABA Agonist
  • For reducing anxiety, promoting sleep,
    anti-convulsant, muscle relaxant
  • Alcohol GABA agonist
  • Anxiolytic
  • Dont drink while taking this medication
  • Alcohol withdrawal ? seizures

19
Alcohol
  • Alcohol acts on many systems
  • Blocks NMDA that is why memory is impaired, and
    why alcohol withdrawal can trigger seizures
  • GABA That is why at low levels alcohol has an
    anxiolytic effect, and at higher levels sedative
    effect
  • Dopamine (mesolimbic system) increases release
    of DA in nucleus accumbens, thus the euphoria,
    addictive power of alcohol

20
Opiates
  • Endogenous opiates secreted in response to
    survival behaviors
  • analgesia
  • positive reinforcement (encourages the survival
    behavior)
  • Exogenous opiates
  • Morphine (opium)
  • Codeine (opium)
  • Heroin (semisynthetic)

21
  • 1897 Mail order advertisement from Sears,
    Roebuck Co. for opium-based drink
  • Early 20th century mothers encouraged to use
    opium syrup to soothe teething pain
  • Narcotic comes from the Greek word, narke,
    meaning stupor and referred
    to any drug that
    induced sleep

22
Opiates administration distribution
  • Administration
  • smoke (Opium, Heroin)
  • intranasal (heroin)
  • intravenous (Heroin)
  • oral, not very good to get high
  • (Codeine, morphine, methadone)
  • Distribution
  • Heroin is 10 times more liposoluble than
    morphine, so
  • it reaches brain faster and at larger
    concentrations, and
  • get transformed into morphine

23
Opioids
morphine
  • Drug Effects
  • Analgesia (morphine)
  • Activates Reward system (addictive power)
  • Inhibits defensive response (e.g., hiding)
  • Antagonist
  • Naloxone
  • Use in the acute treatment of heroin overdose
  • Blocks analgesic effect of placebo

Naloxone
24
Opiates Side effects
  • Most of the risks are secondary to the status as
    illegal.
  • Legal Jail
  • Health HIV, hepatitis C, overdose
  • Financial loss of employment, cost of drugs
  • Few direct problems from chronic use
    (surprisingly)
  • (constipation, bladder cancer, pregnancy)

25
  • Cannabis
  • THC is the active ingredient in marijuana.
  • THC receptor CB1
  • large concentration in hippocampus (memory
    effect)
  • THC stimulates release of dopamine in the nucleus
    accumbens and the ventral tegmental area
  • Long-term damage
  • Cognitive impairments from long-term use appear
    to be subtle.

26
Cannabinoids (THC)
  • There are endogenous exogenous cannabinoids
    (marijuana)
  • They are lipids
  • They mix well in butter (cookies) oil (pesto),
    but not in alcohol or water.
  • They depot in fat tissue thus metabolites can be
    detected in urine long after the psychoactive
    effect
  • Drug Effects
  • Analgesia
  • Sedation
  • Stimulates eating (munchies)
  • Reduces concentration memory
  • Distorts time perception
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