NEUROTRANSMISSION Flashcards
What is the main excitatory neurotransmitter in the central nervous system?
Glutamate
Name four main receptor subtypes for glutamate.
NMDA, AMPA, Kainate, Metabotropic receptors
Are NMDA, AMPA, and Kainate receptors ionotropic or metabotropic?
Ionotropic
Why is glutamate recycling important for neurons?
It maintains optimal neurotransmitter levels in the synapse, prevents overstimulation, and prevents excitotoxicity and neuronal damage
What effect do NMDA antagonists have?
They block the activity of NMDA receptors, involved in synaptic plasticity, memory formation, and various pathological processes
How do NMDA antagonists affect memory function?
Excessive blockade of NMDA receptors can impair memory function
What are some clinical applications of NMDA receptor antagonists?
Treatment of epilepsy, schizophrenia, depression, Alzheimer’s disease
Which conditions is GABA important for regulating?
Epilepsy, anxiety disorders, certain types of movement disorders
How is GABA synthesized and deactivated?
Synthesized from glutamate by glutamic acid decarboxylase (GAD); deactivated through reuptake and degradation by GABA transaminase (GABA-T)
How can a drug be devised to increase GABA levels?
Both GABA transaminase inhibitor and GABA reuptake inhibitor would effectively increase GABA levels in the synapse, enhancing inhibitory neurotransmission
What conditions do benzodiazepines treat?
Anxiety disorders, panic attacks, insomnia, muscle spasms
How do benzodiazepines enhance inhibitory neurotransmission?
They act as positive allosteric modulators of the GABA alpha receptor, increasing the inhibitory effects of GABA on neuronal activity
What is the function of the GABA alpha receptor?
It is a ligand-gated chloride ion channel responsible for fast postsynaptic inhibition
How does vigabatrin affect GABA levels in the brain?
It inhibits GABA transaminase, thereby increasing GABA levels in the brain
What is the function of the GABA beta receptor?
It is a G-protein-coupled receptor that inhibits calcium influx, activates potassium channels, and inhibits neurotransmitter release
What neurotransmitter is associated with the noradrenergic system?
Norepinephrine (noradrenaline)
What functions are regulated by the noradrenergic system?
Attention, arousal, stress responses
What neurotransmitter is associated with the serotonergic system?
Serotonin
What functions are regulated by the serotonergic system?
Mood, sleep, appetite, various physiological functions
What neurotransmitter is associated with the dopaminergic system?
Dopamine
What functions are regulated by dopaminergic neurons from the substantia nigra?
Motor control, affected in Parkinson’s disease
What functions are regulated by dopaminergic neurons from the ventral tegmental area?
Reward, motivation, addiction
What neurotransmitter is associated with the cholinergic system?
Acetylcholine
What functions are regulated by the cholinergic system?
Memory, attention, learning
What are autoreceptors?
Receptors located on the presynaptic neuron that regulate the release of neurotransmitters
What is the function of autoreceptors when activated?
They inhibit cell firing and transmitter release at the terminal regions
What are the autoreceptor subtypes for serotonin (5-HT)?
5-HT1A, 5-HT1D (also known as 5-HT1B)
What are the autoreceptor subtypes for dopamine?
D2 or D3
What are the autoreceptor subtypes for noradrenaline?
α2
How does reserpine affect noradrenaline (NA) levels?
Depletes NA stores by inhibiting vesicular uptake, interfering with packaging into synaptic vesicles
How does amphetamine affect noradrenaline (NA) levels?
Enters synaptic vesicles, displaces NA into cytoplasm, increases leakage of NA, elevating extracellular levels
How does cocaine affect noradrenaline (NA) levels?
Blocks reuptake of NA, leading to increased levels in synaptic cleft, prolongs action and enhances effects on postsynaptic receptors
What type of neurotransmitter is noradrenaline?
Monoamine
What are the actions of noradrenaline on receptors?
Both inhibitory (acting on β receptors) and excitatory (acting on α and β receptors)
How is noradrenaline terminated after release?
Neuronal uptake and degradation by monoamine oxidase (MAO)
Where are the main cell bodies for noradrenergic neurons located?
Locus coeruleus
During which state are noradrenergic neurons particularly active?
Wakefulness
What effect do drugs like amphetamine have on noradrenaline activity?
Increase alertness and exploratory behavior
In which brain regions does noradrenaline have a high density of receptors?
Brainstem, hypothalamus, medial temporal lobe
What functions is noradrenaline involved in?
Arousal, wakefulness, exploration, mood regulation, blood pressure regulation, addiction, gambling behaviors
What is the association between low levels of noradrenaline and depression?
Low levels of noradrenaline are associated with depression
What type of neurotransmitter is dopamine?
Monoamine
How does dopamine primarily affect central neurons?
By acting on potassium (K+) channels to inhibit them
What are the two main families of dopamine receptors?
D1 receptors (including D1 and D5 subtypes) and D2 receptors (including D2, D3, and D4 subtypes)
Where are D3 receptors primarily located?
In the limbic system, but not in the striatum
How is dopamine neurotransmission terminated?
By degradation through the enzyme monoamine oxidase (MAO) and reuptake into presynaptic terminals
Name two main pathways in the brain involving dopamine.
From the substantia nigra to the basal ganglia and from the midbrain to the limbic cortex
What roles does dopamine play in physiological and behavioral functions?
Movement control, addiction, stereotypy, hormone regulation, vomiting
What neurological disorder is associated with dysfunction in the dopamine system?
Parkinson’s disease
What psychiatric disorder is associated with abnormalities in dopamine function?
Schizophrenia
What type of neurotransmitter is serotonin (5-HT)?
Monoamine
How many known subtypes of serotonin receptors are there?
14
Which subtype of serotonin receptors is excitatory and found in the limbic system and cortex?
5-HT2 receptors, particularly 5-HT2A
Where are 5-HT3 receptors located, and what are they associated with?
Located in the medulla and associated with vomiting
What is the termination process for serotonin neurotransmission?
Degradation through the enzyme monoamine oxidase (MAO) and reuptake into presynaptic terminals
Name three physiological and behavioral functions regulated by serotonin.
Mood regulation, psychosis, sleep-wake cycle
What psychiatric disorder is associated with imbalances in serotonin levels?
Anxiety and depression
Which serotonin receptor subtype is targeted by antipsychotic medications?
5-HT2A
What role does serotonin play in pain pathways and migraine?
Inhibits pain pathways and can act synergistically with opioids to alleviate pain
What are the main histamine receptor subtypes and their functions?
H1 receptors (involved in arousal) and H3 receptors (presynaptic, constitutively active)
What are the functions of histamine in the central nervous system?
Regulation of sleep-wake cycles and involvement in vomiting
Name two purines and their receptor subtypes.
Adenosine (acts on A1 and A2A/A2B receptors) and ATP (acts on P2X receptors)
What are the functions of adenosine in the central nervous system?
Regulation of sleep, pain modulation, neuroprotection, addiction, seizures, anticonvulsant effects
Name three types of opioid receptors and their functions.
μ, δ, and κ receptors. Functions include pain modulation.
What neuropeptides act on tachykinin receptors, and what are their functions?
Substance P (acts on NK1 receptors), neurokinin A (acts on NK2 receptors), and neurokinin B (acts on NK3 receptors). Functions include modulation of pain pathways.
What type of receptors do endocannabinoids act on, and what are their effects?
Endocannabinoids act on CB1 receptors, inhibiting GABA and glutamate release. They are involved in various functions such as vomiting, pain, anxiety, and weight loss.
What are the receptor subtypes for melatonin, and what is its role?
MT1 and MT2 receptors. Melatonin is involved in regulating sleep and circadian rhythmicity.
What are some clinical applications of melatonin agonists?
Melatonin agonists are used for jet lag and insomnia.
