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
The Grand Scheme

CNS Structure and Function

Methods of research in Behavioural
Psychopharmacology

Neurotransmitters and the CNS

Neurodegenerative disorders
And then………….

Drug dependance and addiction

Alcohol, CNS stimulators, cannabinoids,
opiates

Anaesthetics

Affective disorders

Anxiety disorders

Schizophrenia
Psychoactive drugs

Found throughout recorded history

Opium poppy


Alcohol


Ancient Mesopotamia – laws to control
drinking
Peyote cactus (mescaline)


Neolithic burial sites
Native Americans
Amanita mushroom

Vikings
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
Psychoactive Drugs: 1000s of drugs –
only a few main CLASSES
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
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
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)
Divisions of the Nervous System
Rest and digestion
Fight and flight
Sensory afferent neurons

Sensory (afferent: “towards”)

Chemoreceptors

Mechanoreceptors

Nociceptors

Photoreceptors

Thermoreceptors
Polysynaptic Reflex
Effectors:
Conscious or
unconscious
PROCESSING
Muscles
Glands
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: >450ms

Reaction time  Information processing

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

Brain capillaries

Intercellular clefts

IC clefts closed

Fenestrations

(tight junctions)

Pinocytotic vesicles

Fenestrations absent

Pinocytotic vesicles rare

“Glial feet” extensions of
astrocytes surround
capillaries
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
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
Regions of the Brain
Telencephalon

Cerebral cortex

Limbic system

Moods, emotions,
learning,memory

Basal ganglia

Voluntary
movement
The Limbic System
Basal Ganglia: dopamine
(corpus
striatum)
(mesencephalon)
Metencephalon and myelencephalon
(medulla) of hind brain

Cerebellum

Pons/medulla = brainstem

Vasomotor, cardiac centre, respiratory centre,
vomiting, cough

Brainstem death (o.d. CNS depressants)
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
Neurones

100 trillion
(1012)

Each neuron
connects to
1000 – 10000
others

1g cortex = 109
synapses

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