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HBIO4 > Drugs & Perception
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Drugs

Monoamine neurotransmitters

  • Examples
    • Catecholamines - dopamine (DA), noradrenaline (NA), adrenaline (ADR)
    • Serotonin (5-HT)
    • Histamine
  • Dopamine
    • Stimulates the limbic system
    • Limbic system is the reward system - it controls emotion, motivation, appetite
    • Many drugs can affect the limbic system by the release of dopamine
  • Cocaine (stimulant)
    • Inhibits re-uptake of dopamine from presynaptic neurones
    • Dopamine remains in synaptic cleft
    • Continues to stimulate postsynaptic neurones
    • Stimulates sympathetic (vasoconstriction, euphoria, …) and limbic system
  • LSD (hallucinogen)
    • 5-HT receptor agonist (mainly subtype 2a)
      • Stimulation causes hallucinations
    • Dopamine agonist

THC receptor

  • Marijuana/Cannabis bind to cannabis (THC) receptors
  • THC receptors prevents the release of inhibitory neurotransmitters
  • Lack of inhibitory neurotransmitters causes the release of dopamine

ACh receptor

  • Nicotine is an agonist at the acetylcholine (ACh) receptor
  • Stimulates sympathetic nervous system
    • Increases heart rate, blood pressure, breathing rate
    • Increases reaction time
    • Increases energy levels
  • Releases dopamine

Neurones and nerve impulses

Sensory and motor neurones

  • Sensory                neurone
    • Activated by sensory input
    • Dendrites form a long dendron (impulse towards cell body)
    • Cell body is found in root cell ganglion
    • Axon carries impulses away from cell body
  • Motor neurone
    • Dendrites extend from the cell body (no dendron)
    • Axon carries impulses away from cell body
    • Innervates muscles
  • Myelinated axon is surrounded by Schwann cells (myelin sheath)
    • Increases speed of conduction

Resting Potential

  • MEMBRANE IS POLARISED: inside of axon is more -ve than outside
  • A resting potential of -70mV is maintained by
    • Negatively charged proteins/large anions inside axon
    • Membrane more permeable to K+ than to Na+ / K+ ions move out faster than Na+ ions diffuse in
    • Sodium/potassium pump / Na+ ions pumped out faster than K+ ions pumped in
  • Electrochemical gradient determines movement of ions
    • K+ cannot move down its conc. gradient
    • Build up of positive Na+ outside membrane repels K+
  • Imbalance of negative ions causes potential difference/voltage
    • Cl- cannot move down its conc gradient
    • Negatively charged proteins in cytoplasm repel Cl-

Action Potential

  • Stimulus reaches threshold
  • Voltage-regulated sodium channels open / influx of Na+ / down electrochemical gradient / +ve feedback
  • Depolarisation / inside becomes +ve / membrane potential reverses
    • //Depolarisation opens sodium channels in adjacent membrane
  • Potassium channels open (slower than Na+ gates) / diffusion of K+ ions out of neurone
  • Repolarisation
  • Sodium channels close
  • Hyperpolarisation due to overshoot in movement of K+out of the cell
    • //Membrane potential is lower than resting potential
    • //Interior of the cell becomes -ve \ membrane is more permeable to K+ ions than to Na+ ions
  • Sodium-potassium pump restores RESTING POTENTIAL
  • [GRAPH] Highest positive membrane potential is the action potential

All-or-nothing nature

  • Once action potential starts, it travels to a synapse
  • Stimulus must cause sufficient movement of Na+ and K+ to depolarise the membrane and
  • cause an action potential
  • Threshold stimulus → impulse that causes an action potential
    • Stimulus transmits an impulse at a constant and max strength
    • Transmission is independent of any intensity of the stimulus
    • High frequency of impulses / more amount of sodium entry / more ATP
  • Subthreshold stimulus → stimulus weaker than a threshold stimulus
  • Summation → series of subthreshold stimuli cumulate to cause an action potential

Refractory Period

  • Represents a time during which the membrane cannot be depolarised again
    • During repolarisation and hyperpolarisation
    • Membrane is impermeable to Na+ ions / sodium ion channels closed
    • Sodium ions cannot enter axon
    • K+ ions move out as membrane is more permeable to K+ ions
    • Membrane becomes more negative than resting potential
  • Nerve impulses can only travel in one direction
    • Action potential can only depolarise the membrane in front
    • Membrane behind is recovering from refractory period (previous action potential)
  • Limits frequency with which neurones can transmit impulses

Speed of Conductance

  • Impulses travel faster in myelinated neurones → SALTATORY CONDUCTION
    • Schwann cells prevent diffusion of ions
    • Flow of current between adjacent nodes of Ranvier
    • Thus, depolarisation only at nodes of Ranvier
    • Action potential jumps from node to node
  • Temp affects speed of conduction of impulses
    • Higher temp increases rate of diffusion of ions
  • Impulses faster in an axon with larger diameter
    • Small cells / large surface area:volume ratio / ion leakage weakens membrane
    • Myelin stops ion leakage \ diameter only important for unmyelinated neurones

Synapses - where neurones communicate

Structure

  • Synaptic cleft (gap) of 20μm separates two neurones at a synapse (junction of 2 neurones)
    • Presynaptic membrane is at the end of a neurone
    • Postsynaptic membrane is at the next neurone in the chain
  • Synaptic knob of a presynaptic neurone contains
    • Neurotransmitters in small vesicles
    • Mitochondria to produce ATP needed for neurotransmitter synthesis
  • Neuromuscular junction
    • Presynaptic neurone connects with muscle
    • Postsynaptic membrane is called the motor end plate

Synaptic Transmission

Unidirectional

  • Neurotransmitter always travels from pre- to postsynaptic membrane
  • Thus, flow in one direction only, action potential only in postsynaptic neurone

Summation

  • Several presynaptic neurones release neurotransmitter
  • Cumulative effect reaches a threshold to depolarise postsynaptic membrane
  • E.g. rod cells when they synapse with relay neurones in the retina
  • Spatial summation
    • Several impulses arrive at one neurone via several synapses
    • Cause sufficient depolarisation / open sufficient sodium ion channels
    • For threshold to be reached
  • Temporal summation
    • Several impulses arrive at same neurone via same synapse
    • Threshold → action potential

Inhibition

  • More inhibitory postsynaptic potentials IPSPs than excitatory postsynaptic potentials EPSPs
  • Reduces membrane potential / makes more negative
  • Hyperpolarisation of postsynaptic membrane
  • Cancels effect of action potential when several synapses

Mechanisms of Transmission

  • Nerve impulse reaches synaptic knob/presynaptic membrane/neurone
  • Depolarisation opens Ca2+ gates / calcium ions enter
  • Ca2+ causes vesicles containing neurotransmitter to fuse with membrane
  • Release of neurotransmitter / into synaptic cleft / by exocytosis
  • Diffuse across synaptic cleft
  • Neurotransmitter binds to specific receptors in postsynaptic membrane
  • Sodium channels open / sodium ions enter
    • Depolarisation of postsynaptic membrane
    • Threshold causes an action potential along postsynaptic neurone
  • Neurotransmitter are quickly removed from the postsynaptic membrane
    • Diffuse out of the synaptic cleft
    • Taken up by presynaptic membrane by endocytosis
    • Enzymes break down neurotransmitters into inactive substances

Effect of Drugs

  • Postsynaptic membrane
    • Act as agonists → bind to and stimulate receptors
    • Act as antagonists → blocks receptors and prevent binding of neurotransmitter
  • Stimulate release of neurotransmitters from presynaptic membrane
  • Inhibit destruction of neurotransmitter in synaptic cleft