Drugs can affect how we perceive the world around us

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