Neurotransmitters Flashcards
Main amino acid neurotransmitters
glutamate
GABA
glycine
glutamate
main excitatory transmitter in CNS
GABA
main inhibitory transmitter. Synthesized from glutamate and causes Cl- influx
glycine
inhibitory transmitter in the brain stem, spinal cord and retinal tissue
Main Monoamines
Da
NE
5Ht
the NT involved in learning, and may cause parkinsonian like symptoms if depleted
DA
NT invovled in arousal, fight or flight
NE
the NT involved in mood control, and released by the raphé nuclei
5HT
the NT involved with CNS modulation and muscle contraction
Acetyl choline
Nitric Oxide
promotes vasodilation and CNS modulation
the main NT in taste cells, and co transmitter in many diverse synapses
ATPs
a ____ is a small 10 AA length chain that modifies the effects of other neurotransmittesr on the target receptor
Neuropeptides.
Dales Principle
individual neurons may release more than one transmitter but they typically release the same combination of substances into the synpase
5 main types of neuropeptides
1) ADH/Vasopressin
2) Oxytocin
3) Substance P
4) Dynorphin
5) Neuropeptide Y
ADH
Controls fluid balance and reproductive behavior
Oxytocin
induces labor, controls reproductive behavior
neuropeptide that modulates pain
dynorphin
substance P
modulates pain SENSITIVITY
Neuropeptide Y
regulates appetite.
mechanism and effecs of MDMA. Side effectS?
causes serotonin to stay in the synapse longer. More intense mood effects; increase pleasure, feelings of closeness. Causes depression afterwards due to serotonin depletion. research shows it irreversibly damages serotonergic axons; may cause chronic depression and impulsivity and impaired verbal memory in chronic users.
Neuromodulation
the alteration of a neurons response to a specific synapse or neurotransmitter. substances can act as neuromodulators.
Ionotropic receptors
ligan gated ion channels that open up when activated by the binding of a neurotransmitter. Ions then flow through the central pore.
example of an ionotropic receptor
AMPA: opens in response to glutmate and allows Na+ to flow into cell (excitatory)
Metabotropic receptors. Which receptor causes change the fastest? Metabotropic or ionotropic?
no cental power, but they are COUPLED to nearby ion channesl and can employ SECOND MESSENGER SYSTEMS as an intermediary step. They are slower to take effect but they are longer lasting
4 main glutamate receptors
AMPA and NMDA and kainate (open in response to kainic acid) and metabotropic glutamate receptor: category of metabotropic receptors that act as AUTORECEPTORs.
why is NMDA receptor so special
because it is both ligand gated and voltage gated.
It requires glutamate for activation (ligand gated) in addition to indirect ligands such as glycine, polyamines and Zn2+, and the channel is alos blocked by magnesium at negative membrane potentials. therefore, NMDA central pore only lets positive ions through when glutamate is bound to the receptor and when the membrane is POSITIVELY (potentiated)?
which ions flow through NMDA? What happens to the inside of the celL?
primarily calcium. Ca2+ influx can activate second messenger systems that play a role in plasticity.
NMDA receptor contains _____ suunits that each contain a ___ ___ ___
4 subunits that each contain a glutamate binding site.
Extrasynaptic receptor
when receptors on post syn cell is very far away from the pre syn cell that releases the neurotransmitter.
pre syn neurons reach extrasynpatic receptors via : ___ ___
volume transmission: release of neurotransmitter into the EXTRACELLULAR SPACE rather than synapse in order to DIFFUSE to the far away receptor.
pro and con of volumetric transmission.
it can influence many neurons at once
con: cannot communicate detailed info like synaptic transmission.
a ____ is required for transmitter synthesis but it itself is not a neurotransmitter
precursor.
how is acetylcholine made? what enzyme catalyzes this reaction?
acetyl coA precursor reacts with choline to create acetylchloine and CoA. Reaction is catalyzed by Cholineacetyltransferase.
2 main cholinergic projections:
1) brainstem projection system: stems from the DORSOLATERAL PONTINE SYSTEM and projects into brain stem structures like the LOCUS COERULEUS, Retricular formation, rapheé nuclei, thalamus, cerebellar nuclei and tectum (mid brain component)
2) Forebrain system: the limbic branch and the cortical branch.
limbic branch: cholinergic neurons branch from the MEDIAL SEPTUM to reach HIPPOCAMPUS, amygdala, hypothalamus and olfaction regions.
cortical branch: cholinergic neruons branch the NUCLEUS BASALIS and projects into the neocortex.
acetyl choline esterase
separates Ach into choline and acetate. choline can get transported back into the presynaptic cell and be used for making more Ach later
How can you prevent choline from being transported back into the pre synaptic cell?
using the drug called Hemischolinium, which INACTIVATES the transporter.
2 main types of ACh receptors. What stimulates them and inactivates them?
1) nicotinic: found in PNS (neuromuscular junctions) . IONOTROPIC and stimulated b nicotine and blocked by curare.
2) muscarinic: METABOTROPIC RECEPTORS stimulated by muscarine and blocked by atrophine.
HOw does the botulism toxin work?
ACh antagonist. causes paralysis by PREVENTING Ach release at terminal buttons. (often in PNS)
how does black widow venom work?
ACh AGONIST. Causes contraction of muscle by facilitating the Ach Release
What is Hemmicholinium
a drug that stops the choline transporters and prevents Ach recycling/synthesis
what is neostigmine
inhibitor of acetylcholinesterase. Prevents Ach breakdown
what is atropine
blocks the muscarinic receptors. Therefore causes paralysis in CNS
What is curare
blocks nicotinic receptors. Therefore causes paralysis in PNS
Main chatecholamines, main indolamines. Main effect differences between the two groups.
catecholamines: DA NE and Epinephrine –> activational effect on behavior
Indolamines: Serotonin.–> calming effect on behavior.
LDOPA
the levorotatory form of lDOPA, the precuros of catecholamine synthesis. Is a DA agonist, can be used as a treatment for parkinsons
Parkinsons typically is caused by degeneration of the _____ system
nigrostriatal dopamine system, involving the degeneration of the basal ganglia.
main causes of parkinsons
1) unknown etiology
2) viral encephalitis
3) brainstem trauma (ex/ boxing)
monoamines are formed from the AA ____. List how Norepinephrine is formed
monoamines is formed from tyrosine.
Tyr —> L DOPA via tyrhydroxylase
LDOPA –_> Dopamine via DOPA decarboxylase
DA –> NE via dopamine betahydroxylase.
3 main dopaminergic systems
1) nigrostriatal pathway
2) mesolimbinc pathway
3) mesocorical pathway.
what is the nigrostriatal pathway?
dopaminergic pathway in which neurons orginate at the substantia ngra and terminate in the CAUDATE NUCLEUS AND PUTAMEN. damage to this system causes parkinsonian like symptoms because of the decrease in DA in the Basal ganglia, which is associated with this pathway.
what is the mesolimbic pathway
dopaminergic pathway in which neurons originate in the Ventral Tegmental area and terminate in the Nucleus Accumbens, amygdala and hippocampal regions. It is the main system invovled in pleasure and reward system of the brain adn thus affects motivation.
what is the mesocortical pathway
dopaminergic pathway that originates from VTA and terminates in the PFC.
precursor loading
using intermediate molecuels invovled in the synthesis of a neurotransmitter in order to facilitate neurotransmitter synthesis.
ex/ using LDOPA to promote DA synthesis in the early stages of Parkinsons.
AMPT
blocks tyrosine hydroxylase (therefore no LDOPA can be made); interferes with catecholamine synthesis
Reserpine
causes DA to leak into the post synaptic space by interfering with vesicle formation.
Apomorphine
A drug that blocks dopamine autoreceptors at low doses; at higher doses blocks postsynaptic receptors as well.
(autoreceptor antagonist)
presynaptic autoreceptor
lives on the presynaptic cell. when it release an NT, some NT can bind to the autoreceptor on the cell that released it and precents the further relase. therefore, it plays a role in the negative feedback system.
MAO:
monoamine oxidases. Degrade monoamines in the synaptic space.
What is an MAOI and provide an example
MAOIs prevent monoamine degredation and allows Da/Ne and 5HT to stay in the synapse longer. An example of an MAO is Deprenyl, which blocks MAOB, and is a DA agonist.
chloropromazine
blocks D2 receptors (prevents DA binding); used to treat schizophrenia. Treats the positive symptoms of schizophrenia. May cause tardive dyskinesia (uncontrollable impulses like lip smacking)
methyl phenidate. What disorder is this used in?
inhibits the reuptake of DA, allowing DA to exert effects longer. Used in ADGD: it increases the dopamine in the frontal cortex, allowing for increased activation of the frontal cortex and allows for attention maintenance.
Difference between epinephrine and norepenephrine
epinephrine: secreted by adrenal medulla, used in sympathetic NS. CANNOT CROSS the blood brain barrier and thus only affects the PNS.
NE: synthesized by neurons and used an NT in the CNS. Large amounts can be found in the PONS (Locus coereleus).
norepinephrine projections
starts from the locus coeruleus: dark colored group of noradrenergic cell bodies located in the PONS. Projections then stem everywhere in the brain.
Axonal varicosity
enlarged regions along the length of an axon that contains synaptic vesicles and can release NT or Neuromodulators. Can exert effects into multiple locations.
Idazoxan:
a drug that blocks presynaptic noradrenergic Alpha 2 receptors. Acts as an AGONIST. Facilitates the release of NE.
serotonin is an ____ type of monoamine
indolamine
PCPA:
inhibits tryptophan hydroxylase and interferes with 5HT production
Prozac inhibits the reuptake of 5HT (agonist). What is this drug classified as?
SSRI
Why does it take a while for antidepressants such as fenfluramine to work?
fenfluramine stimulates the release of 5HT. There is a lag because the body it trying to maintain homeostasis and is using compensatory mechanisms to initially work against the drug
where is the serotonin projection?
starts from the raphé nuclei and substatia nigra and projects around the brain
outline serotonin synthesis
tryptophan to 5-hydroxytryptophan vis tryptophan hydroxylase
5HTP to 5HT via 5HTP decarboxylase
LSD is a ____ receptor agonist
5HT2a receptor agonist
MDMA is an ___ and ____ agonist.
Ne and 5HT agonist.
4 types of glutamate receptors
1) NMDA
2) AMPA
3) KAINATE
4) METABOTROPIC GLUTAMATE RECEPTOR
glycine and zinc ions are ___ ___ for NMDA receptors, and facilitate NMDA opening when glutamate is present.
INDIRECT AGONIST
T/D: NMDA can open if there is enough glycine and zinc ions, even if glu is not present
false. glu is the direct agonist and must be present in order to activate the ligan gated NMDA channesl
long term potentiation. What NT is involved?
LTP: occurs via Ca2+ influx from NMDA receptor activation. Causes increased sensitivity to stimulation in post synaptic cells. Enhances learning and long term memory storage.
direct agonist vs indirect agonist
direct agonist: beinds directly on receptor site and acts like a neurotransmitter
indirect agonist: increases and enhances the amount of neurotransmitter effects, but does not bind on receptor site to act as an NT itself.
How does PCP work?
Binds to a specific PCP binding site on NMDA receptor and serves as an indirect antagonist, resulting in NO NMDA activation.
What receptors are affected by benzodiazepnies?
they are indirect agonists of GABAa receptors in order to act as anxiolytic drugs.
4 main binding sites of a GABA receptor
1) benzodiazepine site
2) picrotoxin site
3) barbituate and eTOH site ( deadly)
4) Steroid site.
allylglycine
inhibits GAD, the enzyme involved in GABA synthesis
muscumol:
direct agonist. Binds to the binding site of the GABAa receptor.
bicuculline
direct antagonist for GABA binding site on the GABAa receptor. reduces GABA’s inhibitory effects
____ is the main inhibitory transmitter in the lower brain stem and spinal cord
glycine
strychnine:
direct antagonist for glycine receptor
what is an endorphin and what is the main type of endorphin
endogenous opioids. A peptide that is secreted by the brain. Maintypes are enkephalins
naloxone
a drug that blocks opiate receptors
the ___ is the primary site for opiate reward effects
mu receptor.
the opiate binds to the ____ zone and stimulates the ___ zone, which exerts the effect
the opiate binds to the AFFINITY zone and stimulates the ACTIVITY zone, which exerts the effect
increase in opiate stimulatory effects depends on how activated the ____ zone is
activity zone
differences between heroin, buprenorphine and nalozone in terms of their ability to fill an activity zone
heroin completely fills the activity zone, whereas buprenorphine only partially fills the activity zone. naloxone binds to the affinit zone but does not fill the activity zone at all, which is why it can be used to treat opioid overdoses (blocks receptors and does not exert mu stimulatory reward effects, causing direct withdrawal).
the substances also bind to the mu receptor with different affinities. heroine is considered to be a full receptor agonist.
an____ is an endogenous lipid ligand that binds to naturally occuring CB receptors
engocannabinoid
THC
active ingredient in marijuana, activates the CB1 receptors in the brain.
anandimide
cannabinoid discovered endogenously and in chcolate.
FAAH
enzymes that destroy anandimide after anandimide is removed from the synapse back into the cell vai transporters.
Rimonabant
a drug that blocks CB1 receptors
MAFP
a drug that inhibits FAAH; prevents the breakdown of anagamide. there fore its a cannabinoid agonist
AM1172:
inhibits the reuptake of anadamide
Location of Cb1 and CB2 receptors
Cb1 receptors: in CNS
CB2 receptors: in PNS.
what type of receptors are cb receptors?
they are METABOTROPIC. They are coupled with secondary messenger systems.
beneficial effects of THC
glaucoma treatment, asthma and antinausea
negative effects of THC
inhibition of visuomotor coordination, decreased attentio and memory, evidenced decrease in IQ with prolonged use in adolescents.
Adenosine
a nucleoside that acts a neuromodulator and decreases arousal
how does caffeine work?
it acts as an adenosine antagonist and blocks adenosine receptors. Facilitates wakefullness.
Nitric Oxide
gas produced by cells in the nervous system that acts as a neuromodulator and method of communication.
Nitric oxide is produced by ____
nitric oxide synthase
how can nitric oxide synthase be deactivated by?
L-NAME
other function of nitric oxide
can elicit 2nd messenger activating systems (ex/ guanylyl cyclase to form cGMP)
