Neuropharmacology

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Neuropharmacology

• Effects of drugs on the nervous system
• Brain is seat of integration of nervous activity
  and consciousness
• Drug effects on CNS affects behaviour, moods,
  cognitive ability, motor activity, sensory
  interpretation
• Psychopharmacology

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The Grand Scheme

• CNS Structure and Function
• Methods of research in Behavioural
  Psychopharmacology
• Neurotransmitters and the CNS
• Neurodegenerative disorders

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And then.

• Drug dependance and addiction
• Alcohol, CNS stimulators, cannabinoids, opiates
• Anaesthetics
• Affective disorders
• Anxiety disorders
• Schizophrenia

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Psychoactive drugs

• Found throughout recorded history
• Opium poppy
• Neolithic burial sites
• Alcohol
• Ancient Mesopotamia laws to control drinking
• Peyote cactus (mescaline)
• Native Americans
• Amanita mushroom
• Vikings

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Curative or Medicinal Effects

• Coca leaves (cocaine)
• S.American silver mines increase mental and
  physical vigilance in low PO2 environment
• Tea (caffeine)
• General tonic for the sages of Ancient China
• Indian snake root (rauwolfia serpenina)
• Treatment for manic excitement, hallucinations,
  delusion
• Reserpine depletes dopamine stores

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Psychoactive Drugs 1000s of drugs only a few
main CLASSES
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Common Mechanisms

• CNS stimulants eg amphetamine (amine), cocaine
  (alkaloid)
• Alertness ?, faster behavioural responses
• Stimulate release of dopamine, inhibits its
  inactivation
• Most CNS stimulants boost dopamine and/or
  adrenaline

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CNS depressants

• Eg alcohol, barbiturates
• Feelings of sleepiness, impaired psychomotor
  functions
• CNS depressants affect the GABA (?
  amino butyric acid) receptor
• GABA-ergic drugs inhibit neuronal activity

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Drugs ve and ve effects

• Alcohol (aggression, antisocial behaviour,
  criminal behaviour)
• Cocaine (aggression, suspicion)
• Antidepressants (drowsiness, dry mouth)
• Antipsychotics (drowsiness, dry mouth etc)
• Tolerance (adaptive change in CNS)
• Dependance (no benefit only satisfy craving etc)

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Divisions of the Nervous System
Rest and digestion
Fight and flight
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Sensory afferent neurons

• Sensory (afferent towards)
• Chemoreceptors
• Mechanoreceptors
• Nociceptors
• Photoreceptors
• Thermoreceptors

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Polysynaptic Reflex
Effectors Muscles Glands
Conscious or unconscious PROCESSING
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Reaction Times vary with complexity of task

• 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
• Choice reaction time task gt450ms
• Reaction time ? Information processing
• Sensitive to drug effects
• CNS stimulants reduce reaction time
• CNS depressant drugs retard reaction time

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The Brain (Cerebral cortex)
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Cerebrospinal Fluid (CSF)
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CSF-filled subarachnoid space
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Typical vs Brain Capillaries
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Blood Brain Barrier selectively permeable (not
impermeable)

• Typical capillaries
• Intercellular clefts
• Fenestrations
• Pinocytotic vesicles

• Brain capillaries
• IC clefts closed
• (tight junctions)
• Fenestrations absent
• Pinocytotic vesicles rare
• Glial feet extensions of astrocytes surround
  capillaries

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Blood-Brain barrier not complete

• Area Postrema (or CTZ chemical trigger zone)
• Medulla of brain stem
• vomiting centre
• Median eminence of the hypothalamus
• Hypothalamic neurotransmitters ? anterior
  pituitary

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Limited permeability and drug action

• Physostigmine readily crosses barrier
• Useful for treating intoxication from pesticides
• Increases availability of acetylcholine
• Neostigmine is excluded from brain
• increases Ach only peripherally
• Neostigmine can treat myasthenia gravis without
  CNS side effects, but not pesticide induced
  intoxication

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Regions of the Brain
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Telencephalon

• Cerebral cortex
• Limbic system
• Moods, emotions, learning,memory
• Basal ganglia
• Voluntary movement

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The Limbic System
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Basal Ganglia dopamine
(corpus striatum)

(mesencephalon)
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Metencephalon and myelencephalon (medulla) of
hind brain

• Cerebellum
• Pons/medulla brainstem
• Vasomotor, cardiac centre, respiratory centre,
  vomiting, cough
• Brainstem death (o.d. CNS depressants)

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Ascending Reticular Activating System

• ARAS fibre bundle runs through core of
  brainstem into thalamus
• Maintains arousal
• 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

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Neurones

• 100 trillion (1012)
• Each neuron connects to 1000 10000 others
• 1g cortex 109 synapses
• Lost at 20000 per day

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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

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Formation of Myelin Sheath
CNS
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Axonal Transport

KINESIN
DYNEIN
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Action Potential All or Nothing
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The Neural Code

• Discharge frequency dependant upon stimulus
  intensity
• Action potential must be re-set before another
  can be triggered
• Refractory period

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The Resting Potential
Differential permeability Electrostatic
gradient -70mV (inside vs outside)
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Saltatory Conduction
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Summation of IPSP/EPSP
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THE SYNAPSE
presynaptic
postsynaptic