neurotransmitters and neuromodulators

acetylcholine (ACh)

first NTM to be discovered/identified

acetylcholine

generally excitatory NTM mainly involved in movement, learning, memory, sleep, and dream (attention, arousal, anger, aggression, sexuality, thirst)

what is the function of ACh in the PNS?

motor control (movement)/stimulates muscles

what is the function of ACh in the CNS?

facilitates learning and memory

acetylcholine

can be inhibitory depending on type of receptor —> major ntm of parasympathetic NS

acetylcholine

prevalent in hippocampus

hippocampus

facilitates formation of new memories

acetylcholine

associated with memory loss in Alzheimer’s disease.

Alzheimer’s disease

involves impairment of memory and other cognitive functions

Effect of less ACh in the forebrain

memory loss

acetylcholine

is released at every synapse at which a motor neuron terminates at a (skeletal) muscle fiber, and activates the motor neurons that control and contract the (skeletal) muscles

neuromuscular junction

last neuron ends at muscle fiber

botulinum toxin

produced by clostridium botulinum

clostridium botulinum

bacteria that can grow in improperly (dented) canned food

botolinum toxin

extremely potent poison —> teaspoonful could kill the world’s entire human population

botulinum toxin

prevents or blocks the release of ACh at nerve-muscle synapses and thus can cause death when the respiratory muscles (muscles for breathing) become paralyzed.

muscles for breathing

diaphragm, intercostal muscles, abdominal muscles

botulinum toxin

botox injections

why can’t you lie down for long periods 6 hours after botox?

to prevent it from going to CNS

is botulinum agonist or antagonist?

antagonist —> prevents ACh release at nerve-muscle synapse

how does botulinum toxin cause death?

lower ACh means lower contractions = muscles paralyzed —> can’t breathe

black widow spider venom

stimulates the release of ACh

black widow spider venom

fatal but less toxic than botulinum toxin

how is black widow spider venom fatal?

more ACh = higher contractions —> muscles tire and respiratory failure occurs

is black widow spider venom agonist or antagonist?

agonist —> stimulates ACh release

cramping as a form of high contractions

not normal = electrolyte imbalance in action potential; potassium

pesticides / insecticides / nerve gases developed for warfare

destroys the enzyme AChE (acetylcholinesterase)

pesticides / insecticides / nerve gases developed for warfare

uncontrolled build-up of ACh —> normal synaptic transmission becomes impossible.

is pesticides / insecticides / nerve gases developed for warfare agonist or antagonist?

agonist —> destroys AChE —> more ACh

effect of too much and continuous ‘violent’ muscle contractions caused by ACh build-up

may also cause difficulty in breathing and eventual death

Norepinephrine (NE) / Epinephrine

keep us alive —> has to do with life function

Norepinephrine (NE) / Epinephrine

monoamine (catecholamine) produced mainly by neurons in the brainstem (pons, medulla oblongata and thalamus)

Norepinephrine (NE) / Epinephrine

excitatory neurotransmitter —> mainly: energy, arousal, vigilance (stress, mood, learning, memory, sleep and eating)

Norepinephrine (NE) / Epinephrine

regulates both physical and psychological-mental arousal

Norepinephrine (NE) / Epinephrine

raises the heart rate and blood pressure

Norepinephrine (NE) / Epinephrine

mental focus and attention, and it is responsible for increase in vigilance

Norepinephrine (NE) / Epinephrine

adrenaline

effect of too little Norepinephrine (NE) / Epinephrine

depression

effect of too much Norepinephrine (NE) / Epinephrine

hyperactivity/anxiety

Norepinephrine (NE) / Epinephrine

associated with bipolar mood disorder —> any drug that causes it to increase or decrease is correlated with an increase or decrease in the individual’s mood level.

Cocaine and amphetamines

prolong the action of NE by slowing down its reuptake process, or stimulating its release —> receiving neurons are activated for a longer period of time

are cocaine and amphetamines agonists or antagonist?

agonist

what are amphetamines?

stimulants, used for weight loss and ADHD

Lithium

speeds up the reuptake of NE —> depression

is lithium an agonist or antagonist?

antagonist —> facilitates reuptake —> depression; bipolar meds (?)

how is NE/E produced in the brain?

locus coeruleus, pons, reticular formation —> projected to —> cerebral cortex, midbrain, hippocampus

epipen

epinephrine in a pen —> used for allergies/anaphylaxis

example of how NE/E works to increase vigilance

bronchioles: constricts and relaxed to breathe more during emergency (widens)

meds used for allergies

antihistamine, nebulizer (steroids), epinephrine

Dopamine (DA)

similar/related to epinephrine

Dopamine (DA)

monoamine (catecholamine) mainly involved in motor control and reward motivation (attention, learning, memory, emotional arousal)

Dopamine (DA)

associated with the reward-motivation mechanism of the brain (rewarding sensations —> addiction)

what type of NTM is Dopamine (DA)

monoamine (catecholamine)

Dopamine (DA)

regulates the pleasurable emotions, and drugs like cocaine, heroin, nicotine, opium and even alcohol —> increase its level for which the user of such drugs feels good

Dopamine (DA)

inhibitory neurotransmitter that controls posture and voluntary movements of the body

undersupply of Dopamine (DA)

can lead to Parkinson’s disease

Parkinson’s disease

• neurological disorder disrupting coordinated movement

• degeneration of the nigrostriatal system (substantia nigra/midbrain) —> white color rather than the normal black

• is characterized by weakness, tremors, lead-pipe rigidity, poor balance (shuffling gait), difficulty in initiating movements, reduced voluntary movements, stoop posture with loss of arm swing when walking (poverty of movements), masked face and slurred speech

what is used to treat Parkinson’s

L-DOPA: precursor/agonist of DA —> can pass across the blood-brain barrier and enter into the CNS

Dopamine (DA)

implicated as the neurotransmitter that might be involved in schizophrenia

schizophrenia

mental disorder whose symptoms include hallucinations, delusions, perceptual disorders, addiction, bizarre behaviors and disruption of normal, logical thought processes and produced by overactivity of dopaminergic neurons

oversupply of DA

can lead to development of schizophrenia or schizophrenic reaction

Chlorpromazine

drug used to treat schizophrenia

Is chlorpromazine agonist or antagonist?

antagonist —> blocks dopamine receptors and alleviate the symptoms

Dopamine (DA)

works on the sympathetic nervous system —> increased heart rate and blood pressure, when used medically (fight or flight)

Serotonin (5-HT)

monoamine (indolamine)

5-hydroxytryptamine

full name of serotonin

Serotonin (5-HT)

synthesized from the tryptophan (amino acid)

Serotonin (5-HT)

Serotonin (5-HT)

inhibitory neurotransmitter that is considered as the ‘worry’ chemical in the brain

Serotonin (5-HT)

control and regulation of emotion, impulses, and dream (mood, anger, aggression, anxiety, pain, eating or appetite (and vomiting), arousal or wakefulness, sleep, body temperature and sexuality

anorgasmia

a sexual dysfunction characterized by persistent difficulty or inability to achieve orgasm despite adequate sexual stimulation and desire

low sertononin

leads to depression, suicidal thoughts, obsessive-compulsive behaviors, mood disorders, anxiety and insomnia

Serotonin (5-HT)

It prevents dreaming in the waking state

Fluoxetine (Prozac)

• treat depression, some forms of anxiety disorders and obsessive-compulsive disorders

• first antidepressant

• makes you happier

is Fluoxetine (Prozac) antagonist or agonist?

agonist —> inhibits the reuptake of 5-HT

Fenfluramine

• appetite suppressant in the treatment of obesity

• decreases appetite (binging)

is Fenfluramine agonist or antagonist

agonist —> causes/stimulates the release of 5-HT as well as inhibits its reuptake

MDMA

• ecstasy

• agonist —> stimulates its release and inhibits its reuptake

LSD

• stimulates 5-HT receptors

• agonist

how is 5-HT produced

raphe nuclei (brain stem), cerebral cortex, spinal cord

relationship between binging and depression

generally, more depressed people tend to binge as an outlet

Glutamate (Glu) (glutamic acid)

• most commonly found excitatory neurotransmitter in the CNS

• present in more neurons of the CNS than any other neurotransmitters

what type of NTM is glutamate

amino acid

Glutamate (Glu)

enhances the action potential or the transmission of information in the brain

Glutamate (Glu)

mainly related with functions like learning and memory

NMDA (N-methyl D-aspartate) receptor

• one subtype of glutamate receptor

• role to play in the process known as long-term potentiation (LTP) —> memory

• hippocampus —> rich in this receptor (ACh and Glu)

• LTP takes place in the hippocampus

Glutamate (Glu)

mainly associated with Alzheimer’s disease

effect of excess of glutamate

• toxic for neurons

• related with ALS (amyotrophic lateral sclerosis) and seizures (excitotoxicity)

seizures

• too much Glu —> too much activity —> AP fired continuously

• convulsing —> uses a lot of energy (high metabolic rate)

• part of the brain is hyperactive

• increase in temperature can cause this in kids

  • adult hypothalamus is developed enough to regulate temperature compared to kids

• worn out and possibility of death due to consumption of energy

• need to control so it won’t globalize in the brain

• olden times: cut corpus callosum so it won’t spread to other hemisphere (isolate)

ketamine

• anesthetic

• NMDA receptor antagonist —> lower activity

• liquid sedation —> not usual sedation

  • dissociated from reality

  • eyes open but blank, awake but not awake

drugs can be administered in different ways

• has to do with onset

• how fast and how much the effect

• injecting/intravenous: direct effect —> faster than oral and snorting

• snorting: drug goes to mucus membrane —> faster than oral

  • effect slower and lasts longer

• intramuscular: slower than intravenous, slower effect

• generally: faster onset, shorter duration (gets eliminated faster)

how is Glutamate produced?

hippocampus, amygdala, basal ganglia

Gamma-aminobutyric acid (GABA)

amino acid NTM created from glutamate

Gamma-aminobutyric acid (GABA)

• main inhibitory neurotransmitter in the CNS —> wide distribution throughout the brain and spinal cord

• occurring in 30-40% of all synapses

• concentration within the brain is 200-1000 times greater than that of the monoamines or ACh

Gamma-aminobutyric acid (GABA)

• inhibits action potential

• inhibits the CNS by decreasing the activity of the neuron

• balance and offset excitatory messages

• slows down neuron activity in order to prevent excitation which could lead to seizures

effect of increase GABA

less action potential

GABA agonist

drug used for seizures to counter glutamate

causes of epilepsy

abnormality in the biochemistry of GABA-secreting neurons or in GABA receptors

how do seizures occur?

• Neurons in the brain are greatly interconnected.

• Without the activity of inhibitory synapses these interconnections would make the brain unstable

• Neurons would excite their neighbors —> until most of the neurons in the brain would be firing uncontrollably

Epilepsy

neurological disorder characterized by the presence of seizures