1. A5: Neuropharmacology

2. Synaptic Transmission

3. Synaptic Transmission

4. Initiating an Action Potential

5. Neurotransmitters
Neurotransmitters can be either excitatory or inhibitory.
Excitatory neurotransmitters – promote an action potential to occur in the post synaptic neuron
Inhibitory neurotransmitters – make it more difficult for an action potential to occur in the post synaptic neuron

6. Excitatory Post-Synaptic Potential (EPSP)
Generates an action potential in the post synaptic neuron
A neurotransmitter is released from the pre-synaptic neuron and causes the post-synaptic neuron to open its Na+ channels.

7. EPSP
If the post synaptic neuron was originally at a resting potential of -70mV, when Na+ enters the neuron, the membrane potential increases to become close to zero (it’s depolarized!)
If threshold levels are reached, this is the generation of an action potential in the post synaptic neuron and thus the transmission of a nerve impulse from one neuron to another

8. Inhibitory Post-Synaptic Potential (IPSP)
This is when a post synaptic neuron is inhibited from producing an action potential (and thus continuing a nerve impulse)
HOW?
Inhibitory neurotransmitters make the post synaptic neuron more negative

9. IPSP
Post synaptic neurons open it’s Cl- channels, allowing Cl- to enter the neuron
This hyperpolarizes the membrane (makes it more negative)
Ie: a membrane potential lower than -70mV
(Another method could be the opening of K+ channels to cause K+ to move out of the neuron which would also make the neuron more negative)

11. IPSP
This makes is more difficult to generate an action potential on the post-synaptic membrane because the resting potential is now further away from the threshold value.
The means that a nerve impulse will (likely) not be transmitted from neuron to neuron

12. Summation of EPSP and IPSP
Decision making is the summation of EPSP and IPSP signals
More than 1 pre-synaptic neuron can form a synapse with the same post-synaptic neuron
If the sum of the signals is excitatory, the axon fires
If the sum of the signal is inhibitory, the axon does not fire.

13. Summation of EPSP and IPSP
If there are more EPSPs than IPSPs, then an action potential will be generated.

15. Slow and Fast Neurotransmitters
The neurotransmitters we’ve discussed so far have all been fast-acting, crossing the synaptic cleft and binding to receptors less than a millisecond after an action potential arrived at the pre-synaptic membrane.
Some neurotransmitters are slow-acting or neuromodulators and take hundreds of milliseconds to act on the post-synaptic membrane.

16. Slow acting Neurotransmitters
Instead of acting on a single post-synaptic neuron, they diffuse into the surrounding fluid and act on groups of neurons.
Ex: noradrenalin/norepinephrine, dopamine, and serotonin are slow acting neurotransmitters.

17. Slow-acting Neurotransmitters
Slow acting neurotransmitters do not affect ion movement across the post synaptic membranes directly but instead cause the release of secondary messengers inside post synaptic neuron which regulate fast synaptic transmission.
In this way they can modulate fast acting neurons for relatively long periods of time.

18. Memory and Learning
Involve changes in neurons caused by neuromodulators.
Neuromodulators release secondary messengers inside the post-synaptic neurons and can promote synaptic transmission by
increasing the number of receptors in post-synaptic membrane
chemical modification to increase the rate of ion movements when a neurotransmitters binds

19. Memory and Learning
The secondary messengers can persist for days and cause what is known as long-term potentiation (LTP), allowing new synapses to form in the hippocampus and other areas of the brain.
This is central from memory and learning.

20. Cholinergic and Adrenergic Synapses
Remember, neurotransmitters are chemicals that allow neurons to communicate with each other.
There are over a hundred different brain neurotransmitters
The two main excitatory neurotransmitters are acetylcholine and noradrenalin.
The two classes of neurotransmitters are cholinergic and adrenergic

21. Cholinergic vs Adrenergic
Ex of Neurotransmitter
Acetylcholine
Released by all motor neurons
Activated skeletal muscle
Noradrenalin
Hormone and a neurotransmitter
Most important role is effect on heart
Also increase blood flow to skeletal muscles and glucose release
System
Parasympathetic
- Ie involved in relaxation
Sympathetic
Ie involved in “fight or flight” reactions
Effect on Mood
Calming effect on mood
Increase alertness, energy, and euphoria

22. Dopamine Secretion Neurotransmitter produced by the brain
It causes you to feel good
Any activity that increases the effect of dopamine is potentially addictive because the individual will want to continue the “good feelings” it creates.

23. You’ve just received a hit of DOPAMINE!

24. Dopamine and Drug Addiction
Many drugs interfere with dopamine and extend the time this substance is found at the synapse, which make us feel good.
In drug addiction, dopamine receptors are constantly stimulated.
Over stimulation, decreases the number of dopamine receptors (desensitization)
As a result, when the drug has worn off, users experience less joy (because less receptors) out of every day events – thus, reinforcing drug use
Also, drug intake needs to be increase to achieve the same “high”

25. Psychoactive drugs
Can affect the brain and personality by either increases or decreasing post-synaptic transmission
Psychoactive drugs affect the level of neurotransmitters
In this way they can increase or decrease post synaptic transmission

26. Actions of Psychoactive Drugs
Enhance the release of a neurotransmitters
Ex: Ecstasy
Increases euphoria, diminishes anxiety
Stop the release of a neurotransmitter

27. Actions of Psychoactive Drugs
Mimic the effect of a neurotransmitter
Ex: LSD, morphine and heroin
Mimic endorphins which are natural pain killers

28. Actions of Psychoactive Drugs
Block the removal of a neurotransmitter from the synapse (and prolong the effect of the neurotransmitter)
Ex: Cocaine
Block the receptors of the neurotransmitter (preventing depolarization or hyperpolarization)
PCP/Angel Dust

29. EXCITATORY DRUGS Encourage synaptic transmission
For many drugs, after frequent use, the number of receptors on the post-synaptic membrane are reduced which leads to a decrease in the affect of the drugs.
Increasing doses are needed to obtain the same affect.
Examples:
Nicotine, Cocaine, Amphetamines

30. Stimulant Drugs
These are drugs that promote activity of the nervous system (by mimicking the sympathetic nervous system)
Make the user more alert, energetic, and self-confident.
Many excitatory drugs are stimulants
Some mild simulants are present in food and drinks such caffeine in coffee, tea, soft drinks
May be prescribed to treat depression and narcolepsy

31. Coffee: ASAP

32. Nicotine
Found in cigarettes
Is both a stimulant and a relaxant

33. Nicotine
Immediately after intake, it acts as a stimulant, it causes an increase in adrenaline which increases heart rate, blood pressure and blood sugar levels.
As a result it may appear to (temporarily) increase concentration
Effect can also reduce appetite

34. Nicotine As a relaxant it mimic acetylcholine
Acts on cholinergic synapses of the body and brain to release dopamine – which causes pleasure and makes it addictive
Nicotine is metabolized quickly, disappearing from the blood stream after a few hours.

35. Nicotine Addiction
Repeated exposure to nicotine results in tolerance (which is why smokers will increase the # of cigarettes they smoke to achieve the same results month to month, year to year)
Within a single day tolerance also builds up and some is lost during the night. The 1st cigarette of the day feels “stronger” and it’s affects last longer compared to the 5th cigarette.

36. Cocaine

37. Cocaine A stimulant made from extracts of the Coca plant
Stimulates the CNS and causes feelings of euphoria, talkativeness, increased mental alertness.
Temporary decrease in need for food and sleep.
Large amounts will cause erratic and violent behaviour

38. Cocaine
Blocks the re-uptake of dopamine, so dopamine accumulates in the synapse
Thus addictive feelings of happiness are created (Cocaine is highly addictive)
It also makes the user feel less tired or hungry and enhances endurance
The “high” that cocaine provides is usually followed by a “crash” when the effect of the drug wears off resulting in depression, irritability, and paranoia

39. Cocaine
Remember, the brain will reduce the number of dopamine receptors when overloaded with cocaine
Thus, when drug has worn off, users experience less joy from everyday life further reinforcing increase cocaine use.

40. Cocaine Videos Drug Free World (8 min)
ASAP Science
For chenchen

41. Amphetamines Stimulate the CNS
cause the release of noradrenaline and dopamine and inhibit their uptake
This leads to increased concentration and performance

42. Amphetamines

43. 10 years of drug abuse

44. Ex Stimulant: Pramipexole
Mimics dopamine.
Binds to dopamine receptors (on post synaptic membrane)
Used for treatment in the early stages of Parkinson’s disease to reduce the effects of insufficient dopamine secretion.
Also used as an anti-depressant
Parkinson’s

45. Inhibitory Drugs Reduce synaptic transmission Many are sedatives
Examples
Benzodiazepines
Alcohol
Tetrahydrocannabinol (THC)

46. Benzodiazepines Tranquilizers which slow down the CNS
Ex: Valium (Diazepam), which can be used to treat anxiety, insomnia, and muscle spasms
They hyperpolarize the post-synaptic membranes so that impulses are not sent
(increase release of neurotransmitter GABA which causes Cl- to enter neuron)

47. Alcohol Depresses the CNS
It reduces social inhibitions and makes the person feel cheerful and relaxed.

48. Alcohol
It causes a receptor of GABA to remain open longer, further hyperpolarizing the postsynaptic membrane
This explains the sedative effect of alcohol
(Also helps to increase the release of dopamine – but not well understood how)

49. Tetrahydrocannabinol (THC)
Found in the Cannabis plant (marijuana)

50. Tetrahydrocannabinol (THC)
Causes relaxation and can act as a pain killer by binding to the endorphin receptors causing hyperpolarization
Often create feelings of lightheadedness and increased appetite.
Other receptors it binds to (cannabinoid receptors) will negative affect mental and physical activities:
Learning
Coordination
Problem solving
Short term memory

51. THC Bind to cannabinoid receptors on the pre-synaptic membrane.
This inhibits the release of neurotransmitter that cause the excitation of post synaptic neurons: thus it is a sedative
Cannabinoid receptors found in various parts of the brain including the cerebellum, hippocampus, cerebrum

52. Tetrahydrocannabinol (THC)
Affects hippocampus of the brain, which is important for short-term memory.
Affects cerebellum (involved in coordination) which causes motor impairment
The impairment of memory and decision making abilities cause students using THC to statistically gain lower grades than those not using it.
Scientific research is not unified either way on THC being addictive or not

53. THC Marijuana and the brain http://www.youtube.com/watch?v=oeF6rFN9org
ASAP

54. Anaesthetics
Act by interfering with neural transmission between areas of sensory perception and the CNS, causing the temporary loss of sensation in all or parts of the body
Local anaesthetics (such as those used by the dentist or when getting stiches) cause numbness in an area of the body

55. Anaesthetics
A patient who has been given a general anaesthetic will normally have no awareness of the medical procedures they have undergone as they are unconscious and lack total sensation.
Inhibit sensory organs as will as signals to motor neurons

56. Drug Addiction
Drug Addiction is the repeated and compulsive use of psychoactive drugs
Can be affected by genetic predisposition, social environment, and dopamine secretion

57. Genetic Predisposition?
Controversial
Studies have shown that if there is one addictive person in a family, there is a greater chance of there being another
Believed there is an “addiction gene” that may be turned on in an individual due to environmental context

58. Genetic Predisposition
One example is the DRD2 gene, which codes for the dopamine receptor protein.
There are multiple alleles of this gene and recent studies have shown that people with the A1 allele for the gene consumed less alcohol than those homozygous for the A2 allele for the gene.

59. Social Factors There is an increased chance of addiction for people:
living in an environment where there is substance abuse
Who suffer from a childhood trauma and/or neglect
Psychoactive drugs may become a way for dealing with this

60. Dopamine is AWESOME
Many addictive drugs (including opiates, cocaine, nicotine, alcohol) affect dopamine secretion, causing prolonged periods of high dopamine levels in the brain.
But there are better, safer, more rewarding ways to get your daily dose of dopamine.