Download Physiology 2

Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen
In last lecture we talked about neurotransmitters that act as modulators, the most important modulater is Biogenic
Amines such as : dopamine , norepinephrine , serotonin .
The first one : Dopamine
The source of dopamine in the brain: 1. substanial nigra. 2.ventral tegmental area.
Then it will go to the cortex in three pathways :
1. substanial nigrastriatum (part of the basal gangliaregulates the motor system,
(nigrostiatal pathway)
2. Ventral tegmental arealimbic system(mainly to the nucleus accumbens)related
to the emotions especially pleasure emotion and the reinforcement because we redo things
we happy to do.
(mesolimbic pathway)
3. Ventral tegmental areacortex (mainly frontal), the most importantrelated to
thinking, decision making and social interaction.
Dysfunction in the first pathwaymotor is destroyedParkinson disease.
Dysfunction in the second pathwayemotions are disrupted
Cocaine has the same idea of the second pathway; when someone takes cocainethe second pathway will be
activateddopamine is activated and will activate the nucleus accumbenswhich will enhance the pleasure
feelingaddiction will occur for repeating it all over again.
For more clarification : if we had and exam , and we studied very hard and got high mark in that exam , we would feel
happy , so nucleus accumbens is activated by dopamine (which is also activated by our happiness ) and then we’ll
always study hard because nucleus accumbens is activated by studying hard.
Now, over activation of this pathway will lead to hallucinationwhich is one of the
symptoms of schizophrenia.
*Schizophrenia has positive and negative symptoms, positive like hallucination and
negative like anhedonia.
Anhedonia: means that nothing makes the patient happy or desire anything, and can do
no social interaction.
Dysfunction of the 3rd pathwaydecrease in exploring, decrease in social interaction, no
enhancement of happiness or working and depressionanhedonianegative
symptoms of schizophrenia.
Increase in dopaminepositive schizophrenia symptomsdecreased by dopamineantagonist or D2-agonistnegative schizophrenia symptoms.
So we can’t control the schizophrenia accurately.
The transporter of dopamine is affected by two molecules: cocaine and amphetamine, these molecules inhibit the
function of the transporterwhich will cause the accumulation of dopamine in the synaptic cleft (increase in
concentration), so those are very effective drugs.
Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen
The second one : Norepinephrine
The cell bodies of neurons that release nor epinephrine are located in an area in the brain stem which is
called "nucleus locus coeruleus" .
It is a slow neurotransmitter ( modulator )
As we said previously , dopamine are affected by cocaine and amphetamine , but here there is another state,
norepinephrine are affected by amphetamine ( same as dopamine ) , but there is another drug affects
norepinephrine only ( not dopamine ) , this drug is called Desipramine .
How norepinephrine generates a response for any stimuli ?
Stimuli (Zy lma el Dr 5b6 3la el 6awleh w 5lana ne97a ) Activation of locus coeruleus release of
norepinephrine in the brain attention
If locus coeruleus is sensitive to any small stimuli, it'll release more epinephrine than
needed and this would keep the patient aware with extra attention causing him a
stress disorder, such as: anxiety.
Norepinephrine works on types of receptors : β1 receptors , α2 receptors
In addition to the function of norepinephrine in enhancing attention , it will also affects mood regulation ,
learning and memory .
Learning and memory , attention stimuli  activation of posterior part of prefrontal cortex  connects to α2
receptors  increase releasing of norepinephrine  if there was any defect  ADHD ( attention deficiency
hyperactivity disorder ) , anxiety may occurs
Mood regulation  activation of frontal cortex (area on brain are responsible for personality)  connects to : β1
receptors  releasing of norepinephrine  if there was any defect on the receptor  decreasing
noreepinephrine  bad mood may lead to Depression
Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen
Nor epinephrine goes to many subcorticals such as : limbic system that is related to our emotion ,so , if there is
higher norepinephrine in these locations our energy level will be higher , this is called psychomotor active
If there is little norepinephrine the energy level and emotions will be lower , so this is called psychomotor inactive (
retardation )
The third one : Serotonin
serotonin is synthesized from the amino acid " Tryptophan"
Tryptophan is an essential amino acid, we get it from diet since we can't produce it in our bodies. This
means that the synthesis of serotonin depends on the presence of tryptophan so this is the rate limiting
step .
serotonin is releases from region in the brain stem that is called
raphe nucleus ( rapha always refers to serotonin only )
serotonin as other neurotransmitter goes to all regions in the brain and it is the denser neuromodulator in the
brain, and it is the most abundant. serotonin has 21 receptor and they discovered more in the last few years
.these receptors are divided into families , each of them operate in a certain way .
You should memorize these receptors , but you do this easily by
following these steps :
5HT 3 : Works through ion channels
5HT1 inhibitory ( inhibits cAMP )
5HT2 : Works through PLC system
Other receptors rather than which are mentioned above
stimulates cAMP ( excitatory )
5HT1A , 5HT1B , 5HT2B are receptors located on presynaptic
nerve cell membranes or on the serotonin neuron itself, to regulate the release of the neurotransmitter
Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen
Serotonin works through 17 receptors and controls most of the functions of the brain : mood, sleep, sexuality,
impulsivity, aggression, stress, drug abuse. It's related to many diseases and disorders: Depression,
Schizophrenia, OCD (obsessive compulsive disorder), Eating Disorders, and Autism.
There are lots work on serotonin receptors such as Antipsychotics ( you don't memorize the drugs in the
slide , Ra7 tmor 3lena bl pharma in details )
We can notice that there is a combination between norepinephrine , dopamine, serotonin , each one affects the other ,
so new antidepressant drugs have more than one active site , so , they will work on these three amine system i.e they
can work on dopamine and serotonin for example
Most important treatment and drugs associated with serotoninselectiveserotonin reuptake inhibitor
(SSRI) inhibition for the reuptake or to its transporterincrease serotonin at the synapsesrelive
of the depression .
Neuropeptides :
those are neurotransmitters made out of proteins, proteins are made in the ribosomes in the cell body of the
neuron, and the axon is very long, so making and transferring the neuropeptides to the terminals will take so much
time, it’s released in the synaptic terminal.
So, it’s made in the cell bodyin vesiclesbinds to the motor transport
proteincytoskeletonfinally, to the terminals.
This means I’ll have fewer supplements or less quantity of the protein in the terminal, so normally neuropeptides
are available in small quantities.
So to control that, it should work very effectively and do good amplification, so they all work through , G-protein
receptors, so they are very potent (high efficiency), they are modulators
Sometimes we can see that neuropeptides are available with other neurotransmitters such as : glutamate ,
Acetylcholine , etc .
The most important family of neuropeptides is the oboid :
Those are large family and very important in pharmacology because they are strong pain killers ( analgesic)
But before talking about these pain killers , we must talk a little bit about pain :
Pain: is one type of sensations, and it is the oldest, and is transferred to the brain through the ALS (slow), more
than one level affect the pain before it reaches the cortex, and the first level is the spinal cord, and to all the sub
cortical levels, that’s why pain is very associated with emotions which is the sub cortical responsibility.
Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen
There are some terminology related to the pain ( you should memorize them jay so2al 3lehom in the exam)
The pathway starts from the norepinephrine, from the pain receptors (nociceptor receptors or free nerve ending),
they detect pain by changing the signals from chemical to neuronal signals, and those chemicals are: tissue
damage, cell death, inflammation, trauma, etc.
So the pain is detected by those receptors and goes to the ALS pathway to the cortex, but also it sends many
branches through all the sub cortical regions.
Pain goes to the thalamus then cortex in a way that it is faster than the way which pain passes through it to
reach subcortical regions
After that , the pain go to region is called periaquaductal grey ( modulator to the
pain) then to locus correlus (it sends ascending to the cortex and descending to the spinal
cord)
There are two neurotransmitter that can send signals to the spinal cord : norepinephrine , serotonin
We said that the upper levels controls the lower levels, and pain awakes the upper level to pay attention, and
that’s one of the reflexes job, which means that I can ignore or delete the pain reflexes
Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen
So we need pathways to control the pain even more, and that’s why we have the descending control of the pain,
relive the pain, ignore the pain, or even change the mean of the pain.
The first one is the cortex: usually it doesn’t go directly to the spine (sometimes it can), so it goes to the sub
cortical, what goes down to the spinal cord -depending on what the cortex wants, can increase or decrease the
pain.
The second one is subcortex : through hypothalamus will connect to the parts beneath it in the brain stem
and will affect the pain perception, usually to decrease the pain , so , that's why pain is linked with emotion to
try avoiding pain as much as possible .
The last two are the periaquiductul grey and the locus cerrelus, receive innervations from the pain to do an action
like regulated pain, one way to regulate the pain is to descend down and affect how we feel the pain, mainly the
cortex is responsible for doing that, so we can say that job of these two parts is to inhibit the pain.
They are 3 types (we only going to mention 2): 1.enkephalon. 2. Endorphin.
Encephalon is the smallest, the least known and least distributed in the brain, binds to an oboid receptors (sub
family), its cell body is located mainly periaquaductal grey.
periaquaductal grey takes the pain and descend back down to the spinal cord, so that’s how enkephalon regulates
the pain.
One way to ignore the pain is by blocking the pain from reaching the cortex by blocking the ALS pathway (by
inhibiting the synapse) to stop it from reaching the upper level, by inhibiting the pathway.
They can work alone sometimes, but usually they need a controller from above to tell them block the synapse
coming from a pain , the pathway is coming from the periaquiductal grey, and encephalon neurons won’t work if
they were too long, so they try to be short, so instead of going to the spinal cord they will go to the raffia nucleus
to send the information to the encephalon neuron there to delete the pain.
Raffia nucleusserotoninencephalon inhibition of the synapses no transmission won’t
reach the cortexno pain felt.
Note : we can ignore the pain, because the analysis in the state of our mind decide if there is a pain or not ,
so , sometimes you can forget that you have a pain and concentrate on another thing .
Note : We can relieve the pain by giving blocker to pain receptor , but this way is very dangerous because
the pain receptor is very important for lots of things , so, the better way to relieve the pain is give non
steroidal anti inflammatory drugs to inhibit chemical signal such as : inflammation through prostaglandin ,
trauma, tissue damage etc .
GOOD LUCK 
Physiology 2
Sheet #9
Dr Loai Zgoul
Done By : Maher Shaheen