4) Neurotransmitters & Psychopharmacology Flashcards
Which 2 neurotransmitters carry out most synaptic communication
Glutamate- excitatory
GABA/ glycine (in spinal cord)- inhibitory
Both secreted by terminal buttons
What is psychopharmacology
The study of drug effects on the nervous system
What is an antagonist drug
A drug that opposes/inhibits the effect of a neurotransmitter on a postsynaptic cell
What is an agonist drug
A drug that facilitates the effect of a neurotransmitter on a postsynaptic cell.
How can the rate of neurotransmitter synthesis be increased
Administering a precursor, so acts as an agonist
What controls neurotransmitter synthesis
Enzymes. So drugs that inactivate an enzyme serve as antagonists
How do drugs effect storage and release of neurotransmitters?
A drug molecule binds to a site on a transporter and inactivates it, as it is occupying the same where enzymes usually work. Since nothing can be synthesised, the vesicle is empty and nothing is released when the vesicle fuses with the presynaptic membrane (Serves as an antagonist)
Once some drugs bind to the postsynaptic receptor, what 2 effects can it have?
Serve as a:
direct agonist/antagonist =
> drug that binds directly onto the receptor of interest
Indirect agonist/antagonist=
drug attaches to a binding site on a different postsynaptic receptor, which facilitates/inactivates action of the receptor of interest.
In what 2 ways can drugs effect reuptake/neurotransmitter destruction
1) Interfere with the action of transporter molecules responsible for reuptake of neurotrans molecules back into the terminal buttons of the presynaptic molecule. It does so by blocking and inactivating them
2) Binds with enzyme activation sites which prevents the process of destroying excess neurotransmitters molecules in the cleft, since the binding sites have been occupied with the drug
What do both ways of effecting reuptake/destruction of neurotransmitter have in common?
BOTH of them prolong the presence of neurotransmitter in the synaptic cleft, so serve as AGONISTS
Placebo is..
an inert substance instead of the physiologically active drug, used as an experimental control for an administered drug
Placebo effect is..
The behavioural effects observed of taking/not taking a drug (feelings of getting better on the placebo).
Helps to conclude if any actual changes are caused by the drug.
Nocebo effect is..
Patient feeling worse after even when no effect should have occurred.
Where is the neurotran ACh (Acetylcholine) secreted from?
By the EFFerent nerves axons in the CNS.
Also found in parasympathetic branch of ANS
What is ACh’s key roles?
- ALL muscular movement accomplished by ACh release.
- Involved in REM sleep regulation, memory, perceptual learning
Who discovered ACh
Otto Loewi
Describe the 2 types of ACh receptors, what stimulates them and what blocks them
1) Nicotinic receptor:
ionotropic (direct), stimulated by nicotine
It is blocked by curare (poison serves as muscle relaxant/paralysis).
It acts at the neuromuscular junction between nerve cells and muscles
2) Muscarinic receptor:
Metabotropic (indirect), produces the parasympathetic nerve effects of heart, smooth muscles, glands
Stimulated by muscarine, blocked by atropine (prevents ACh from depolarising the post-synaptic membrane, stops impulse generation to this cell)
Explain the first 3 stages of transmission across a cholinergic synapse (ACh present at these types of synapses)
1) AP arrives at the presynaptic membrane, Ca2+ channels open and calcium ions enter the presynaptic neuron
2) Calcium ions cause vesicles to fuse to the presynaptic membrane and then release ACh into the cleft
3) ACh diffuses across the cleft and binds to neuroreceptor sites in post-synaptic membrane
Explain the last 2 stages of cholinergic synapse transmissions
4) Sodium channels open and ions diffuse into post synaptic membrane, causing depolarisation and an AP to fire
5) Ach- ase (enzyme) breaks down ACh, with leftover products diffusing back into presynaptic neuron where ACh is resynthesises using ATP for next transmission
What is the name of the post synaptic membrane at a neuromuscular junction
The muscle fibre membrane is called the sarcolemma.
What does depolarisation of the sarcolemma lead to?
Muscle contraction
Which neurotransmitters belong to the compound family The Monoamines?
Dopamine, serotonin, noradrenaline (norepinephrine) , adrenaline (epinephrine)
They all primarily effect mood and anxiety. What is dopamine more specifically involved with?
Pleasure, with more of this reward chemical sent to the decision making area of the brain, in order to help feed our pleasurable behaviours i.e. food, sex, water
Define addiction
state of engaging in excessive compulsive behaviours, reinforcing a certain behaviour, since it’s pleasurable. Tends to be followed with a loss of control of intake
Define tolerance
state of no longer responding to a drug, so a higher dose in needed in order to achieve the same effect
Define dependence
normal functioning is only achieved through presence of the drug , with physical disturbance apparent when drug is withdrawn
Where in the brain are the addiction/dependence pathways found?
In the mid brain region, just above the start of the spinal cord
Is it possible to have a dependence without an addiction?
Yes, for example needing to take prescribed drugs for a condition otherwise normally functioning can’t be achieved
What is dopamine’s involvement in Parkinson’s disease?
It is a neurological disease affected by a lack of dopamine production + degeneration of the nigrostriatal system.
Effects include tremors, rigid limbs, poor balance
What can treat Parkinson’s ?
L- DOPA amino acid, a direct precursor to dopamine, that facilitates dopamine production
What system does the pleasure chemical Dopamine follow and what structures are involved?
Follows a process in the MESOLIMBIC system
starts at the VTA > ends in nuccleus accumbens, amygdala, hippocampus - all of mid brain
Where is cocaine’s binding site?
The nuccleus accumbens, in basal forebrain
What effect does cocaine have on dopamine ?
Inhibition of dopamine reuptake, by attaching to the binding site and blocking the reuptake pump.
Therefore increased amount of dopamine transmission across the synaptic gap leading to more nerve impulse to the reward system = excitatory behavioural response
What have PET activation scans of metabolic activity in cocaine users shown?
Blood sugar levels reduce dramatically when using cocaine
Which neurotransmitter is responsible for a whole range of things like mood, eating, sleeping, dreaming, pain and arousal.
Serotonin (5-HT)
Describe the rough pathway serotonin takes in the brain
Spread out and across the brain from the raphe nuclei (base of spinal cord in mid brain region).
How does the LSD drug work?
Stimulates the SNS centre and has a serotonin-blocking effect
What common drug serves as noradrenergic and serotinergic AGONIST
MDMA (facilitates adrenaline/serotonin transmission across neurons)
What are some effects of MDMA
Excitatory behavioural/hallucinogenic response, such as elevated mood, heightened perception, reduced appetite
Outline the effect of MD of serotonin neurotransmitters
It blocks the transporter reuptake binding site, so more 5-HT sent to the psot-synaptic receptor binding sites.
(serotonin-enhacing effect)
Aside from depression like feelings and irritability, what are some other adverse effects of ecstasy
Clouded thinking, hypothermia, disturbed behaviour, jaw clenching (gurn)
What long term effects of MD are there?
Degeneration of serotonin nerve terminals, and impairment to verbal and visual memory
Explain the typical cause of mild depression
Low levels of serotonin, leading to feelings of anxiety, insomnia, feelings of worthlessness, fatigue, apathy
How do pharmaceutical drugs like Prozac help with depression?
Increases the amount of serotonin in the brain’s synapses by blocking the reuptake of serotonin into presynaptic cell. Thus, more serotonin crosses to bind to serotonin receptor sites on the postsynaptic membrane in order to activate them and decrease depression like symptoms
Where is Noradrenaline (norepinephrine) found and what does it do?
NE secreted by the adrenal gland in kidney, working alongside adrenaline to give the body energy in stressful situations ‘fight or flight’.
NE inhibiting medication also helps with depression
Where is the neurotransmitter adrenaline (epinephrine) found ?
Hormone secreted in adrenal medulla (of brain)
Which are the most common neurotransmitters (amino acids) in the CNS
Glutamate, GABA and glycine
Which amino acid is the most important excitatory neurotransmitter in brain?
Glutamate
What is the specialised glutamate receptor called?
NMDA- ionotropic (direct)
Which is the most important inhibitory neurotransmitter in brain/ different form in the spinal cord
GABA (in brain), glycine (in spinal cord)
What analogy helps explain GABA’s role
The brake system, with GABA as the brakes. When driving, you need an accelerator but you also need brakes. GABA does this
Why is GABA’s inhibitory effect good?
It blocks out excessive and unneccessary brain activity i.e. like avoiding negative thinking in depression
Tranquilizer drugs like benzos (anxiolytic drugs) work in what way toward GABA receptors?
Works as an indirect agonist, used for it’s sedative, relaxing effects i.e. Valium
