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Neuropharmacology

Effects of drugs on the nervous system

Brain is seat of integration of nervous
activity and consciousness
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Drug effects on CNS affects behaviour,
moods, cognitive ability, motor activity,
sensory interpretation
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Psychopharmacology
The Grand Scheme
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CNS Structure and Function
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Methods of research in Behavioural
Psychopharmacology
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Neurotransmitters and the CNS
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Neurodegenerative disorders
And then………….
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Drug dependance and addiction
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Alcohol, CNS stimulators, cannabinoids,
opiates
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Anaesthetics
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Affective disorders
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Anxiety disorders
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Schizophrenia
Psychoactive drugs
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Found throughout recorded history
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Opium poppy
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Alcohol

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Ancient Mesopotamia – laws to control
drinking
Peyote cactus (mescaline)
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Neolithic burial sites
Native Americans
Amanita mushroom
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Vikings
Curative or Medicinal Effects

Coca leaves (cocaine)
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S.American silver mines – increase mental and
physical vigilance in low PO2 environment
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Tea (caffeine)
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General tonic for the sages of Ancient China
Indian snake root (rauwolfia serpenina)
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Treatment for manic excitement, hallucinations,
delusion
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Reserpine – depletes dopamine stores
Psychoactive Drugs: 1000s of drugs –
only a few main CLASSES
Common Mechanisms

CNS stimulants: eg amphetamine (amine),
cocaine (alkaloid)
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Alertness , faster behavioural
responses
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Stimulate release of dopamine, inhibits
its inactivation
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Most CNS stimulants boost dopamine
and/or adrenaline
CNS depressants

Eg alcohol, barbiturates
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Feelings of sleepiness, impaired
psychomotor functions
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CNS depressants affect the GABA
( amino butyric acid) receptor
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GABA-ergic drugs inhibit neuronal
activity
Drugs +ve and –ve effects

Alcohol (aggression, antisocial behaviour,
criminal behaviour)
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Cocaine (aggression, suspicion)
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Antidepressants (drowsiness, dry mouth)
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Antipsychotics (drowsiness, dry mouth etc)
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Tolerance (adaptive change in CNS)
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Dependance (no benefit; only satisfy craving
etc)
Divisions of the Nervous System
Rest and digestion
Fight and flight
Sensory afferent neurons
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Sensory (afferent: “towards”)
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Chemoreceptors

Mechanoreceptors

Nociceptors

Photoreceptors

Thermoreceptors
Polysynaptic Reflex
Effectors:
Conscious or
unconscious
PROCESSING
Muscles
Glands
Reaction Times vary with complexity of task
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1ms delay for each synapse

Time between input and output increase with the
number of synapses

Monosynaptic “knee jerk” takes around 30ms

Reaction time task: 200ms
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Choice reaction time task: >450ms
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Reaction time  Information processing
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Sensitive to drug effects

CNS stimulants reduce reaction time

CNS depressant drugs retard reaction time
The Brain (Cerebral cortex)
Cerebrospinal Fluid (CSF)
CSF-filled subarachnoid space
Typical vs Brain Capillaries
Blood Brain Barrier –selectively
permeable (not impermeable)

Typical capillaries
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Brain capillaries
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Intercellular clefts
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IC clefts closed
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Fenestrations
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(tight junctions)
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Pinocytotic vesicles
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Fenestrations absent
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Pinocytotic vesicles rare
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“Glial feet” extensions of
astrocytes surround
capillaries
Blood-Brain barrier not complete
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Area Postrema (or CTZ – chemical trigger
zone)

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Medulla of brain stem
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“vomiting centre”
Median eminence of the hypothalamus
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Hypothalamic neurotransmitters  anterior
pituitary
Limited permeability and drug action

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Physostigmine readily crosses barrier

Useful for treating intoxication from pesticides
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Increases availability of acetylcholine
Neostigmine is excluded from brain
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increases Ach only peripherally
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Neostigmine can treat myasthenia gravis without
CNS side effects, but not pesticide induced
intoxication
Regions of the Brain
Telencephalon

Cerebral cortex
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Limbic system
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Moods, emotions,
learning,memory
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Basal ganglia
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Voluntary
movement
The Limbic System
Basal Ganglia: dopamine
(corpus
striatum)
(mesencephalon)
Metencephalon and myelencephalon
(medulla) of hind brain

Cerebellum

Pons/medulla = brainstem
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Vasomotor, cardiac centre, respiratory centre,
vomiting, cough
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Brainstem death (o.d. CNS depressants)
Ascending Reticular Activating System
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ARAS – fibre bundle runs through core of brainstem
into thalamus
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Maintains arousal
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Sedative-hypnotic drugs reduce basic ARAS activity
– sleepiness

Antipsychotic drugs (eg chlorpromazine) reduce
sensory and cortical input to ARAS

Person awake, but less arousable; either by
environmental events or their own thoughts/feelings
Neurones

100 trillion
(1012)

Each neuron
connects to
1000 – 10000
others

1g cortex = 109
synapses
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Lost at 20000
per day
The Neurone

Soma (cell body

Dendrites (and dendritic
spines)

Receive signals from other
cells via a gap called the
synapse

Axons

Single tubular extension
conducts electrical signal
to terminal boutons
Formation of Myelin Sheath
CNS
Axonal Transport
KINESIN
DYNEIN
Action Potential “All or Nothing”
The Neural Code

Discharge frequency
dependant upon
stimulus intensity

Action potential must
be “re-set” before
another can be
triggered

Refractory period
The Resting Potential
Differential
permeability
Electrostatic
gradient
-70mV (inside
vs outside)
Saltatory Conduction
Summation of IPSP/EPSP
presynaptic
THE SYNAPSE
postsynaptic