Psychopharmacology

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Neurotransmitters
precursors
1. produce
AP ? Ca inflow
Pre-synaptic Neuron (axon)
Post-synaptic neuron (dendrite)
synaptic cleft
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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

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Specific Neurotransmitter Systems ( drugs that
affect them)

• Acetylcholine
• Monoamines
• Dopamine
• Noradrenaline Adrenaline
• Serotonin
• Amino Acids
• Glutamate
• GABA
• Opioids
• THC
• Adenosine (caffeine)

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• Receptors for Acetylcholine
• Muscarinic
• Nicotinic

Cholinergic neurons (release Acetylcholine)
1. produce
Pre-synaptic Neuron (axon)
Post-synaptic neuron (dendrite)
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Belladonna (atropine)
curare
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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)

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• 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)
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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?)

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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
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Dopamine release in the nucleus accumbens
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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)

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Overview- neurotransmitters

• Acetylcholine
• Dopamine
• Adrenaline
• Serotonine
• Glutamate
• GABA
• Opioids
• THC (cannabis)

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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

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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

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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

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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

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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

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Opiates

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

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• 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

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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

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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
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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)

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• 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.

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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