Monoamines Flashcards
Biogenic amines include biomolecules with one or more _
Amines
The 5 major biogenic amines discussed are _
5HT NE Epi (adrenalin) DA Histamine
The 3 tyrosine derivative biogenic amines are _
NE
DA
Epi
The vast majority of the biogenic amines are found in what area of the brain? (name, + 3 components)
Brainstem - Medulla, Pons, Midbrain
As opposed to transmitting modality specific information, biogenic amines are thought to _, and have a crucial role in _ and _
Improve signal to noise ratio
Emotion and cognition
The 3 biogenic amines thought to play a crucial role in mood are _. These BAs modulate each other, as well as other NT systems
serotonin
NE
DA
This system is thought to be central to all theories of mental Illness. Additionally, drugs of abuse act directly or indirectly on this system
Central monoaminergic system
There are as many as 12 5HT systems, but majority are clustered along the midline in what nuclei? What are the 2 major subdivisions?
Raphe n.
Ascending and descending
The 5 major components of the serotonergic raphe system are _? From dorsal to caudal
Dorsal raphe (midbrain) Raphe pontis Raphe Magnus Raphe Pallidus Raphe Obscuris
The 5HT system reaches the thalamus, hypothalamus, amygdala, hippocampus and basal forebrain via _ .What 5HT system components participate in this ?
The medial forebrain bundle Dorsal raphe (midbrain) Raphe pontis (pons)
The 5HT system reaches the cerebral cortex via the _ . What 5HT system components participate in this ?
Internal capsule
Raphe magnus
Raphe obscuris
The major components of the descending 5HT system are _. What are their targets?
Raphe magnus - spinothalamic neurons (pain)
Raphe obscuris - motor neurons
This type of 5HT release “sprinkles” neurotransmitter
Extrasynaptic / non-synaptic
All but 1 5HT receptors are of this type. What is the exception
GPCR
5HT-3
6 areas that 5HT is known to project to are?
Cortex Amygdala Hippocampus Striatum Thalamus Hypothalamus
Of the following, which 2 have the highest 5HT concentrations? Which 3 have the lowest?
(Premotor, motor, primary, limbic, association cortices)
Highest - Primary and Limbic
Lowest - Association, premotor, motor
5HT terminates all over the SPC on parasympathetic and sympathetic preganglionic neurons, motor neurons, spinothalamic neurons and interneurons to accomplish what?
Suppress stimuli that would alter behavioral states
5HT neurons show state dependent discharge? When are they highest and when are the lowest?
Highest during wakefulness
Silent during sleep
Sexual behavior and response are _ by 5HT
Inhibited
Neurons from this 5HT system serves as pain modulators by synapsing on _ to modulate 1st and 2nd order neurons
Raphe magnus
Interneurons (Don’t directly respond to pain stim.)
The command system for pattern generators is the _. This is accomplished by synapsing on _ and _
Raphe Obscuris
Interneurons and Motor neurons
While _ initiates compound and stereotypic limb movements, the _ regulates the magnitude and timing
Reticulospinal system
Raphe-spinal neurons
The precursor AA for 5HT is _
5HT is broken down to 5-HIAA by _
Tryptophan
MAO
The 5HT receptor with similar structure to nicotinic acetylcholine receptors is _. It is targeted by ondansetron for anti-emesis
5HT-3
The function of SERT is to _. Inhibitoion would lead to _
Remove 5hT from the synapse
Increased extracellular 5HT
SERT is inhibited by what 2 classes of drugs? What agent is now banned for causing heart valve disease (also targets SERT)?
SRI
TCA (tri-cyclic antidepressants)
Fenfluramines
A way to prevent 5HT loading into presynaptic vessicles is by targeting _. This inhibition results in _
Vesicular transporters
Increased 5HT release via SERT
SSRIs improve depression in what timespan?
Requires up to 2 weeks
Serotonin syndrome is a life threatening emergency. What are the 3 major functions affected?
Cognition (confusion, hypomania, headache, coma)
Autonomics (shivering, sweating, hypertension, tachycardia)
Somatic (myoclonus, hyperreflexia, insomnia)
The major NE producing nucleus is _, located in the _
LC
Pons
The only source of NE in the cortex is _
LC
The LC is a major component of the _ system. What property of the LC allows for rapid signal spreading? If threat is perceived, the LC can activate the _
Direct arousal
Non-synaptically coupled
sympathetic ANS
The _ provides a major input to the LC
Frontal cortex
The LC is a major component of the _ system. It functions in
Direct arousal
Selection of relevant info, maintaining attention
The three components of the direct arousal system, and their NTs are_. These are only active during _
TBN (histamine)
LC (NE)
Raphe (5HT)
Wakefulness
The major component of the indirect arousal system is
Thalamus
The LC sends projections to the dorsal SPC as part of the _ system, causing release of _ from interneurons to _
Endogenous pain system
Enkephalins
Inhibit pain sensation
_ type of LC release of adrenalin is required to focus on new stimuli. If the stimulus is perceived as a threat, the release is now _, leading to activation of _
Phasic
Prolonged
sympathetic ANS
The acute stress response using NA to cause release of _ via the _
Stress hormones
hypothalamus-pituitary-adrenal axis
4 diseases that the LC is implicated in are_
ADHD (tonic firing)
Panic disorder
Mania (exaggerated NA)
Depression (depleted NA)
The precursor AA for NA is _. The rate limiting enzyme is _. All receptors are of what subtype
Tyrosine
Tyrosine hydroxylase
GPCRs
The 2 major subclasses of NA receptors are _ and _. Where are the expressed? (generally)
Alpha receptors (1 and 2): Blood vessels Beta (1 and 2): Cerebral cortex, heart, lungs
NA reuptake is accomplished by _.
NAT
NA catabolism is accomplished by what 2 enzymes? Inhibition has what effect?
MAO, COMT
Increase in synapse, useful for depression
DA is involved in 4 broad classes of disorders
Movement
Psychosis (hyperfrontality in schizophrenia)
Addiction
Depression
The ascending (2) and hypothalamic DA pathways are called?
Nigrostriatal
Mesocorticolimbic
Tuberoinfundibular
The function of DA in the nigrostriatal pathway is _
Facilitate Movement in basal ganglia circuits
The function of DA in the mesocorticolimbic pathway is _
Reinforce rewards
The DA pathway to the hypothalamus is called _. Its function is _
Tuberoinfundibular
Inhibit prolactin release from lactotroph cells
The precursor AA for DA synthesis is _. All receptors are of _ subtype
Tyrosine
GPCRs
The 2 families of DA receptors are _ and _. Their members are _
D1 like (1-5) D2 like (2,3,4)
Antisychotics target _ pathway for the treatment of schizophrenia, thought to be caused by _
Mesolimbic pathway (N. accumbens) Excess DA
Excess DA in the _ contributes to the _ signs of schizophrenia. Excess DA in the _ contribute to the _ signs of schizophrenia
Mesolimbic pathway - Positive signs
Mesocortical pathway - negative signs
The positive signs of schizophrenia are _ (2). The negative signs of schizophrenia are_ (4).
- Hallucinations and delusions
- Avolition, apathy,flat affect, alogia
There is a positive correlation between antipsychotic effect and _ among _ class of antipsychotics
D2 receptor binding affinity
Typical
Atypical antipsychotics target the _ and _ dopamine receptors
D3 and D4
Reuptake of DA is accomplished by _. Inhibition is associated with _
DAT
Psychosis
DA is catabolized by _ and _. Inhibition of these enzymes may result in _ symptoms
COMT
MAO
Psychotic
Inhibition of the nigrostriatal pathway leads to _
Tardive dyskinesia
Inhibition of DA receptors in the mesolimbic pathways is thought to _
Lessen psychosis
The effect of typical antipsychotics on the tuberoinfundibular is _
Increased prolactin secretion from the pituitary
