1. A.5 Neuropharmacology

2. Understandings
Some neurotransmitters excite nerve impulses in postsynaptic neurons, and others inhibit them
Nerve impulses are initiated or inhibited in postsynaptic neurons as a result of summation of all excitatory and inhibitory neurotransmitters received from presynaptic neurons
Many different slow-acting neurotransmitters modulate fast synaptic transmission in the brain
Memory and learning involve changes in neurons caused by slow-acting neurotransmitters
Psychoactive drugs affect the brain by either increasing or decreasing postsynaptic transmission
Anesthetics act by interfering with neural transmission between areas of sensory perception and the CNS
Stimulant drugs mimic the stimulation provided by the synaptic nervous system
Addiction can be affected by genetic predisposition, social environment, and dopamine secretion
Application
Effects on the nervous system of two stimulants and two sedatives
The effect of anesthetics on awareness
Endorphins can act as painkillers
Skill
Evaluation of data showing the impact of MDMA (ecstasy) on serotonin and dopamine metabolism in the brain

3. Excitatory neurotransmitters = stimulate transmission in next neuron
Increase permeability to positive ions (transmitters)
Inhibitory = cause positive ions move out postsynaptic cell
Chemically depresses neuron
Synapse – space between neurons, where chemical message is sent

4. 3. Vesicles containing neurotransmitters fuse with presynaptic membrane
4. Release neurotransmitters into synaptic cleft
2. Reaches axon bulb  Ca+2 rush into end of neuron
1. Impulse moves down presynaptic neuron  action potential
Ions enter or leave when neurotransmitter binds to receptor
5. Neurotransmitter binds to specific receptors on postsynaptic membrane

5. Excitatory Neurotransmission
Generates an action potential
Increase permeability of postsynaptic membrane to positive ions
Example – acetylcholine
Na+, located in synaptic cleft, diffuse into postsynaptic neuron (PSN)
PSN depolarized locally by influx of Na+
PSN develops net positive charge compared to outside cell
Depolarization is how impulse is carried
Na+ continue to diffuse further depolarizing neuron from one area to the next (like a wave)
Action potential formed as membrane depolarization is raised above threshold
Impulse in being carried along nerve

6. Inhibitory Neurotransmission
Inhibits action potential
Causes hyperpolarization of neuron  more difficult for generation of action potential
Inside of neuron becomes more negative
Example – GABA
Causes K+ to move out of PSN
Causes Cl- to move across postsynaptic membrane into cell

7. Neuron receiving end of excitatory and inhibitory stimuli
Neuron sums up signals
If, sum is inhibitory  axon does not fire
If, sum is excitatory  axon fires
Summation of messages  way that decisions are made in CNS

8. Slow Neurotransmitters
Fast Neurotransmitters
Hundreds of milliseconds up to a minute signal time with PSN
1 millisecond transmission time with PSN
Slow-acting NTs act on second messenger molecule
Second messenger is actual NT for PSN
Examples: dopamine, serotonin, acetylcholine

9. Slow-acting NTs (neuromodulators) modulate Fast-acting NTs
Released into cerebrospinal fluid
Regulate efficiency of NT release from presynaptic neuron
Regulate efficiency of PSN

10. Slow-acting NTs affect ability to learn
Tested on Aplysia (marine snail)
Gill retraction (reflex)
Siphon stimulated once, gill retracted
Second slight stimulation, same strong response = learned response
Cyclic adenosine monophosphate (cAMP) – secondary messanger
Protein Kinase (PKA)
Short-term learning process

11. Slow-acting NTs affect ability to remember
Long term memory process requires synthesis of proteins
Activation of genes in neuron nucleus
Proteins change form/function of synapse = memory
1. 5 puffs of serotonin
5. Proteins travel and modify shape of synapse
2. Serotonin connects with receptor
4. Activated adenyl cyclase facilitates change of ATP into cAMP
5. cAMP activates PKA
3. G-protein activated, stimulates adenyl cyclase enzyme

13. Cholinergic
Adrenergic
Neurotransmitter
Acetylcholine (Ach)
Noradrenaline
System
Parasympathetic
Sympathetic
Effect on mood
Calming
Increased energy, alertness, euphoria
Drug increase transmission at synapse
Nicotine
Cocaine and amphetamines
Psychoactive Drugs
Two types of synapses

14. Effects of Drugs on Brain
Alter mood or emotional state
Excitatory drugs (nicotine, cocaine, amphetamines) – increase nerve transmission
Inhibitory drugs (benzodiazepines, alcohol, tetrahydrocannabinol (THC)) – decrease nerve transmission
Use different mechanisms at synapses of brain
Block receptor for neurotransmitter
Block release of neurotransmitter for presynaptic membrane
Enhance release of neurotransmitter
Enhance neurotransmission by mimicking neurotransmitter
Block removal of neurotransmitter from synapse, prolong effect of neurotransmitter

15. Nicotine
Mimics acetylcholine (Ach)
Acts on cholinergic synapses  cause calming effect
Ach, once received, broken down by acetyl cholinesterase
Enzyme cannot break down nicotine
Excites the postsynaptic neuron  begins to fire  releasing dopamine
Gives you feeling of pleasure  ‘reward pathway’ of brain

16. Cocaine
Stimulates transmission at adrenergic synapses
Causes euphoria, alertness
Dopamine released blocks removal dopamine  build up
Causes overstimulation  ‘reward pathway’  euphoria
Feelings:
Euphoria, talkativeness, increased mental awareness
Temporary decrease in need for food or sleep
Large quantities – erratic, violent behavior

17. Amphetamine
Stimulates transmission at adrenergic synapses
Increased energy, alertness
Acts by passing directly into nerve cells (carry dopamine, noradrenaline)
Moves directly into vesicles  released at synaptic cleft
NT normally broken down by enzymes, amphetamines interfere
Synapse  high concentrations dopamine (euphoria), noradrenaline (alertness)  high energy effect (amphetamines)

18. Benzodiazepine
Reduces anxiety, used against epileptic seizures
Modulate activity of GABA  main inhibitory neurotransmitter
GABA binds to postsynaptic membrane  Cl- enter neuron
Increases binding of GABA to receptor  postsynaptic neuron more hyperpolarized
Cl- causes neuron to become hyperpolarized  resists firing

19. Alcohol
Increases the binding of GABA  causes hyperpolarization
Explains sedative effect of alcohol
Decreases activity of glutamate (excitatory NT)
Helps increase release of dopamine (process not well understood)
Appears to stop enzyme break down of dopamine at synaptic cleft
Dopamine works ‘reward pathway’

20. Tetrahydrocannabinol (THC)
Main psychoactive chemical in marijuana
Mimics NT – anandamide
Binds to same receptors
Causes postsynaptic neuron to by hyperpolarized
Role of anandamide not completely understood  may play role in memory functions
May eliminate unneeded information from memory
Marijuana disrupts short-term memory

21. THC
Acts on cannabinoid receptors, affect:
Feelings
relaxed, mellow, panic, paranoia
May dilate pupils causing color perception to be more intense
Learning, coordination, problem solving, short-term memory
Inhibits same neurons as anandamide  no enzyme to break down THC  synapse lasts longer
High concentrations of cannabinoid found in:
short-term memory
controls coordination

22. Withdrawal symptoms opposite of euphoria
Addiction
Alcohol, tobacco, psychoactive drugs, pharmaceuticals
Reason for drugs:
Alleviate symptoms to mental illness
Pleasure
Response:
Body develops tolerance  need more and more for same result
Addiction: chemical dependency on drugs
Drugs ‘rewired’ brain  drug has become essential biochemical
Withdrawal symptoms opposite of euphoria
Anxiety, depression, cravings
Alcohol – cause seizures, delirium tremens (severe shaking)
Inhaled drugs  lung damage
Needles  HIV, Hepatitis B/C, kidney disease

23. Genetically predisposition
Social Factors
Genetic deficiency of dopamine receptors predisposes people to addiction
Determine child’s vulnerability to substance abuse
Family addiction, parenting skills, mental health problems
Behavior
Peer pressure very influential
Culture
Introducing drug into a society that wasn’t present  cause social problems and abuse

24. Dopamine Secretion
Drug addiction – dopamine receptors constantly stimulated
Overstimulation decreases number of receptors, remaining receptors less sensitive desensitization/tolerance
Causes less response
More and more drug is needed  neuroadaptive change
Glutamate – may be more important than dopamine
‘oversee’ learning and memories which lead to cocaine-seeking

25. Anesthetics
Lose consciousness – cannot perceive pain
Affect whole body
Pain signal not sent to CNS

26. Endorphins are CNS NT with pain-relieving properties
Released by pituitary gland during stress, injury, exercise
Small peptides which bind to opiate receptors
Block transmission of impulses at synapses
Bind to receptors of neurons involved in pain perceptions, block release of NT
Opiates, morphine, heroin bind to same receptors – mimic endorphins

27. MDMA (ecstasy) and Serotonin
MDMA structurally related to amphetamine that causes extra serotonin to be released
Neuron 2 is activated by serotonin
Axon 1 releases serotonin into synapse
SERT vesicle on neuron 1 uptakes extra serotonin
MDMA forces extra serotonin into axons to be released (YAY!!)
SERT catches up (Depression!!)

28. MDMA (ecstasy) and Dopamine
Serotonin depletion – SERT receptors empty
Dopamine enters SERT receptors
Dopamine broken down, products toxic to serotonin producing neurons
Neurotoxicity cause long-lasting damage to brain cells, killing them or impairing their function