4 - Catecholamines Flashcards
1
Q
- There are at least __ receptors for 5-HT; most are __
- 5-HT1A receptors are concentrated in the __, __ area, __, and __ Raphe nucleus.
- They reduce cAMP synthesis by inhibiting __ __ (just like D2 and α2 receptors).
- They increase opening of __ __ and membrane __
A
14 | Metabotropic
Hippocampus | Septal | Amygdala | Dorsal
cAMP Synthesis | Adenylyl Cyclase
K+ channels | Hyperpolarization
2
Q
- Reserpine (VMAT blocker) depletes __-__ (it is broken down when not protected in vesicles)
- Terminal autoreceptors directly inhibit __-__ release
- Somatodendritic autoreceptors indirectly inhibit its release by slowing the rate of __ __
A
- 5-HT
- 5-HT
- Neuron Firing
3
Q
- 5-HT3 receptors are located on Peripheral Terminals of the __ __
- Chemotherapy drugs and radiation stimulate release of __-__ in the __, which stimulates vagal 5-HT3 receptors and __ __
- __-___ __ such as Ondansetron (Zofran), Granisetron (Kytril), and Palonosetron (Aloxi) are used to treat the nausea
A
- Vagus Nerve
- 5-HT | Gut | Induces Vomiting
- 5-HT3 Antagonists
4
Q
5-HT release is stimulated by a drug family based on amphetamine
- Para-Chloroamphetamine is mainly used __
- Fenfluramine was prescribed for __ __ in obese patients
- Studies in squirrel monkeys showed that repeated high doses resulted in depletion of __ __ in the brain
- Used in low doses to treat chronic _ _ _ _
A
- Experimentally
- Appetite Suppression
- Serotonergic Axons
- PTSD
5
Q
Adjectival Forms of Catecholamines are (3)
A
- Dopaminergic
- Noradrenergic
- Adrenergic
6
Q
The __ __ secretes __ and __ into the bloodstream where they act as hormones
Neurotransmitter function of __ is relatively minor
A
Adrenal Medulla | Epinephrine | Norepinephrine
Epinephrine
7
Q
Epinephrine and Norepinephrine are also known as __ and __
A
Adrenaline and Noradrenaline
8
Q
- Adrenergic Receptors (adrenoceptors) are __. There are two subtypes, __ and __
- α2-receptors reduce synthesis of __ (like D2 receptors)
- α1-receptors operate via __ __-__ __ (frees up Ca2+ ions in the cell)
- β1- and β2-adrenoceptors stimulate Adenylyl Cyclase and enhance __ __ __ (like D1 receptors)
A
- Metabotropic | α | β
- cAMP (Cyclic Adenosine Monophosphate)
- α1-receptors | Phosphoinositide Second-Messenger System
- Synthesis of cAMP
9
Q
Brain areas involved in __ receive substantial Serotonergic __ and express several 5-HT receptor subtypes
A
Aggression | Innervation (stimulate a nerve; supply energy to)
10
Q
Agonists that activate both α- and β-receptors are used to treat bronchial asthma, but Asthma is more commonly treated with a selective β2-agonist, such as Albuterol (Ventolin), in an inhaler, because Beta-receptors in the airways are __ subtype; the heart has mainly __ subtype. Therefore Albuterol alleviates bronchial congestion without producing __ __ __
A
β2 | β1 | Adverse Cardiovascular Effects
11
Q
Adrenergic Agonists or Antagonists are often used in treatment of non-psychiatric conditions because of the widespread distribution of adrenergic receptors in __ __
A
Peripheral Organs
12
Q
Pain felt in response to a stimulus that is not usually painful
A
Allodynia
13
Q
Some drugs cause release independently of cell firing, like __ and __, which trigger both __ and __ release
A
Amphetamine and Methamphetamine | Catecholamine and Serotonin
14
Q
β1 is the main subtype in the heart; β1-selective antagonists, such as Metoprolol (Lopressor), have fewer side effects.
• β-antagonists (beta blockers) are also used to treat __ __ __. They reduce the physical symptoms, such as __, __, and __ (racing heart)
A
Generalized Anxiety Disorder | Palpitations | Flushing | Tachycardia
15
Q
The α1-antagonist Prazosin (Minipress) blocks α1-receptors that cause blood vessel constriction
The general β-antagonist Propranolol (Inderal) blocks β-receptors in the heart, reducing its contractile force
This makes them both good __ for treating __
A
Antagonists | Hypertension
16
Q
- __are the most common treatment for several anxiety disorders
- The main receptor involved is 5-HT__; the partial 5-HT__ agonist Buspirone (BuSpar) is sometimes prescribed
- Presence or absence of 5-HT__ receptors in Forebrain areas during early postnatal development may alter neural circuitry and expression of __ in adult mice
- Suggests that deficient 5-HT__ receptor activity during a critical developmental period may give rise to later onset of anxiety disorders in humans
A
- SSRIs
- 1A | 1A
- 1A | Postnatal Development | Anxiety
- 1A | Anxiety Disorders
17
Q
An agonist that stimulates both D1 and D2 receptors. Causes behavioural activation similar to that seen with stimulants like __ and __
A
Apomorphine | Cocaine | Amphetamine
18
Q
Locus Coeruleus neurons fire more rapidly during __ than during __
Noradrenergic pathways from the __ to the Medial __ and Medial __ areas are involved in wakefulness
Experiment: α1-receptor agonist Phenylephrine and/or general β-receptor agonist Isoproterenol were injected into the Medial Septal area of rats. What happened?
A
Waking | Sleep
Locus Coeruleus | Septal | Preoptic
Spent more time awake
19
Q
Atomoxetine
A
ADHD Treatment
20
Q
Catecholamine release is inhibited by __ on neuron cell bodies, terminals, and dendrites
A
Autoreceptors
21
Q
Drugs that stimulate autoreceptors inhibit catecholamine release, but conversely, __ __ enhance rate of release
A
Autoreceptor Antagonists
22
Q
The Aversion-Mediating pathway includes input to the VTA from the __ __ (LHb) and Dopaminergic Output from the VTA to the __ __ __ (mPFC)
A
Lateral Habenula | Medial Prefrontal Cortex
23
Q
- If a D2 receptor antagonist, such as Haloperidol, is given to rats on a long-term basis, the rats develop __ __
- If the treatment is stopped and an __ (Apomorphine) are given, these rats respond more strongly than control subjects
- This behavioral supersensitivity may be due to increased density of D2 receptors on postsynaptic cells in the __. A Lack of normal neurotransmitter input causes the neurons to increase their sensitivity via __ __
A
Behavioral Supersensitivity
Agonists
Striatum | Up Regulation
24
Q
The memory-enhancing effects of EPI may be mediated by its ability to increase __ __ __
A
Blood Glucose Levels
25
Breakdown Products
Metabolites
26
Breakdown of Catecholamines by **C**atechol-**O**-**M**ethyl**T**ransferase (COMT) and Monoamine Oxidase (MAO) into Metabolites
* DA metabolite (breakdown product) in humans is __ \_\_ Acid.
* NE metabolites: 3-methoxy-4-hydroxy-phenylglycol (*MHPG*) in the brain and __ \_\_ Acid in the PNS
* The metabolites enter the CSF and the bloodstream and are eliminated with \_\_
HomoVanillic Acid
VanillyMandelic Acid
Urine
27
1. Reserpine administration depletes catecholamines and makes bunnies \_\_
2. Adminitering DOPA to bunnies thereafter makes them \_\_
1. Lethargic
2. Energized
28
Drugs that stimulate autoreceptors, inhibit __ release
Catecholamine Release
29
Cathecholamine Reuptake Transporter-Blocking Drugs:
* __ \_\_ inhibit re-uptake of both NE and __ (\_\_-\_\_)
* NE transporter blockers
* __ an antidepressant
* __ for ADHD
* Cocaine inhibits reuptake of all the mono-amine transmitters: \_\_, \_\_, and \_\_-\_\_
Tricyclic Antidepressants | NE | Serotonin (5-HT)
Reboxetine (Edronax) | Atomoxetine (Strattera)
DA | NE | 5-HT
30
Hormones made by your Adrenal Glands, located on top of your kidneys, and sent into your blood when you're physically/emotionally stressed. Members of this groups all share two chemical similarities: they contain a core structure of *catechol* and a nitrogen-containing group called an *amine*.
Catecholamines
31
What are the Catecholamines? (3)
Dopamine (DA)
Norepinephrine / Noradrenaline (NE)
Epinephrine / Adrenaline (EPI)
32
The second enzyme, AADC, is the same for synthesis of __ and \_\_
Catecholamines | 5-HT
| (Aromatic Amino Acid deCarboxylase)
33
High Levels of __ tend to inhibit TH (negative feedback)
Catecholamine
34
When neurons are firing at a high rate, such as during stress, TH is stimulated and __ \_\_ accelerates
Catecholamine Synthesis
35
Catecolamines primarily broken down by enzymes __ and COMT (\_\_-\_\_-\_\_)
\_\_ metabolized by MOA-A in humans and rodents
\_\_ metabolized in humans by MOA-B but by MOA-A in rodents
Catechol-O-MethylTransferase
NE
DA
36
\_\_ and Risperidone (Risperdal) block 5-HT2A receptors and __ \_\_ receptors
Clozapine | D2 Dopamine
37
Activation of α1-receptors in the PFC has a deleterious effect on cognitive functions
* Increased NE associated with stress increases α1-receptor activation, which can lead to __ \_\_
* NE has a lower affinity for α1-receptors than for the α2-receptor subtype found in high levels in the PFC. Under normal conditions: NE __ PFC function and cognitive tasks by activating α2-adrenoceptors there...
* Cognitive functions are optimized at intermediate levels of PFC noradrenergic activity. This relates to the __ \_\_ Curve/Law
Cognitive Impairment | Facilitates | Optimized | Yerkes-Dodson
38
1. Locus Coeruleus also projects to __ \_\_ (PFC), which has roles in cognitive functions like __ and __ \_\_
2. Activation of α2-receptors in the PFC using selective agonists, such as *Clonidine* and *Guanfacine*, enhances __ \_\_. It helps monkeys to not be fooled by \_\_
1. Prefrontal Cortex | Attention | Working Memory
2. Working Memory | Distractors
39
Ctecholamine Synthesis Steps (4)
Thyrosine
DOPA
Dopamine
Norepinephrine
40
D2 receptors also regulate membrane __ \_\_
In some cells, D2 receptor stimulation activates a __ \_\_ that enhances K+ channel opening
This causes __ of the cell membrane, decreasing the __ and __ \_\_ of the cell
K+ channels | G protein | Hyperpolarization | Excitability | Firing Rate
41
DA and NE systems have several receptor subtypes
The DA autoreceptor is __ subtype
The NE autoreceptor is __ subtype
Mutant mice with no D2 autoreceptors (but normal postsynaptic D2 receptors in non-DA neurons) were more active than controls and more __ to cocaine
D2 subtype
α2 subtype
Autoreceptors | Sensitive
42
DA receptor knockout mice:
1. D1 receptor knockout mice exhibit behavioral abnormalities and deficits in __ \_\_
2. D2 knockout mice show __ \_\_ \_\_
3. Mice with D1 and D2 double knockouts \_\_
1. Cognitive Tasks
2. Impaired Movement | Coordination | Posture Control
3. Die in the second or third week of life
43
1. DA uses five receptor subtypes __ to \_\_
2. All are \_\_. They interact with G proteins and function via __ \_\_
3. __ and \_\_are similar (D1-like receptors)
4. __ \_\_ and __ are a separate family (D2-like receptors)
1. D1 to D5
2. Metabotropic | Second Messengers
3. D1 | D5
4. D2 | D3 | D4
44
Dopaminergic System originates in several cell groups, mostly in the brainstem. Classification system for DA and NE neurons:
1. Cell groups A1 to A7 are \_\_
2. Cell groups A8 to A16 are \_\_
1. Noradrenergic
2. Dopaminergic
45
Ascending Dopaminergic (DA) system is divided into three pathways
1. The __ \_\_ axons from the A9 cell group in the __ \_\_ extend to the __ or \_\_-\_\_
2. The A10 cell group is in the __ \_\_ \_\_. It gives rise to two pathways. Those are:
* __ \_\_ pathway from the VTA to various structures of the Limbic System
* __ \_\_ pathway from the VTA to the Prefrontal Cerebral Cortex
1. Nigrostriatal Tract | Substantia Nigra | Striatum (Caudate-Putamen)
2. Ventral Tegmental Area | Mesolimbic Dopamine | Mesocortical Dopamine
46
Neurons that synthesize NE also have __ \_\_-\_\_ (3rd enzyme in catecholamine synthesis)
Dopamine β-Hydroxylase
47
Evidence from animal studies indicates that NE, EPI, and glucocorticoid hormones modulate the __ of __ \_\_
Consolidation | Emotional Memories
48
Many DA and NE axons form __ \_\_ synapses. Fibers exhibit repeated __ (swellings) along their length, filled with __ \_\_
En Passant (in passing) | Varicosities | Synaptic Vesicles
49
Most 5-HT is located in the \_\_
Some is found in neurons of the __ *Nervous System,* a system of ganglia in the muscle walls of the intestines.
More is synthesized by __ cells using the enzyme TPH1, the non-neuronal form of TPH
Gut
Enteric Nervous System
Enterochromaffin
50
Epinephrine has undesirable side effects, which diminishes its usefulness as a potential __ \_\_, but glucose (or a drug that boosts __ \_\_ \_\_) might be effective
Cognitive Enhancer | Glucose | Blood Glucose Levels
51
* Phasic (“burst mode”) firing of these Serotonergic Neurons must be triggered by __ \_\_ \_\_
* Most research on neurotransmitter regulation of Serotonergic Neuron firing has focused on *Glutamate*, *Acetylcholine*, and *GABA*, but other neurotransmitters help regulate, including \_\_, \_\_, and \_\_
* Excitatory Synaptic Inputs
* DA | NE | Orexin
52
Catecholamines are normally released by __ when a nerve impulse reaches the terminal
Exocytosis
53
\_\_ __ are serious side-effects of antipsychotic and other drugs
Extrapyramidal Effects/Symptoms
54
Blood-borne NE and EPI work with NE released as a transmitter (from sympathetic nerves) to mediate the physiological changes that make up the __ \_\_ __ response, which is comprised of 3 primary effects. What are they?
Fight-or-Flight
* elevated blood pressure and heart rate
* decreased digestive activity
* dilation of blood vessels to skeletal muscles, heart and brain
55
* 1 - (2,5-*DimethOxy*-4-I*odoPhenyl*)-2-*AminoPropane* (DOI) is a 5-HT-\_\_ \_\_
* DOI and related drugs are __ in humans
* The hallucinogenic effects of *Lysergic Acid Diethylamide* (LSD) are believed to stem from its ability to stimulate \_\_-\_\_ \_\_
5-HT2A Agonist | Hallucinogenic | 5-HT2A receptors
56
DA receptor Antagonists suppress exploratory and locomotor behaviour. At higher doses, such drugs can result in \_\_, which is lack of spontaneous movement. Usually associated with D2 receptor *blockers* such as __ but also __ \_\_ such as SCH 23390
Catalepsy | HaloPeridol | D1 Blockers
57
5-HT1A receptor activation improves performance in spatial learning and memory tasks, probably due to their high density in the \_\_
But activation of __ 5-HT1A receptors was shown to impair memory encoding in a contextual fear-conditioning task
Cognition is improved when animals are treated with a 5-HT6 receptor antagonist
The 5-HT6 Receptor Antagonist *idalopirdine* has been tested clinically in patients with __ \_\_
Hippocampus
Hippocampal
Alzheimer’s Disease
58
1. 5-HT1B or 5-HT2C Receptor Agonists, and 5-HT6 Antagonists produce \_\_, or reduced food intake
2. The 5-HT–releasing drug *Fenfluramine* was used to treat obesity, but caused heart valve abnormalities and __ \_\_
3. __ \_\_ __ were caused by activation of 5-HT2B receptors in the heart valve tissue
4. The __ (appetite-reducing) effect could be traced in part, to activation of Hypothalamic 5-HT2C receptors
5. *Lorcaserin* (Belviq), a selective 5-HT2C agonist, was developed to treat
1. Hypophagia
2. Pulmonary Hypertension
3. Cardiac Side Effects
4. Anorectic
5. Obesity
59
\_\_ is an increased sensitivity to stimuli that are usually painful
Hyperalgesia
60
1. Some drugs block pain signals transmitted by the trigeminal nerve, which is responsible for __ \_\_ and __ \_\_ like __ and \_\_
2. Transdermal Sumatriptan (Zecuity) uses ____ to move drug molecules. It uses a __ \_\_ on the skin.
1. Face Sensation | Motor Functions | Biting | Chewing (most complex of cranial nerves)
2. Iontophoresis | Voltage Gradient
61
D1 receptor knockout mice exhibit __ \_\_
Mice lacking D1 receptors (D1–/–) are insensitive to the locomotor-stimulating effects of \_\_
Behavioral Abnormalities | Cocaine
62
1. LateroDorsal Tegmentum to Nucleus Accumbens is the __ \_\_ \_\_
2. Lateral Habenula to Medial Prefrontal Cortex is the __ \_\_ \_\_
1. Reward-Mediating Pathway
2. Aversion-Mediating Pathway
63
One-Trial Passive Avoidance Learning Paradigm is commonly used to evaluate __ \_\_. Longer avoidance = __ \_\_
Memory Consolidation | Better Learning
64
Stress associated with *One-Trial Passive Avoidance Learning* produces increased EPI and glucocorticoid secretion from the __ \_\_
Central noradrenergic neurons also increase NE release in the brain
All of these processes are believed to play some role in __ \_\_ __ \_\_
Adrenal Glands
Passive Avoidance Memory Consolidation
65
*MethyleneDioxyMethAmphetamine* is a recreational drug knwon as
MDMA | Ecstasy
66
MHPG
3-Methoxy 4-Hydroxy PhenylGlycol
67
Mesencephalon
A9 Cell group associated with the...
Caudate-Putamen or...
Mid-Brain
Substantia Negra
Dorsal Striatum
68
Abnormal dilation of blood vessels in the brain contributes to migraine headaches
\_\_ are 5-HT1B/1D agonists [like sumatriptan (*Imitrex*) and zolmitriptan (*Zomig*) that cause __ \_\_ to ease pain
Triptans | Vessel Constriction
69
Drugs that inhibit breakdown enzymes:
1. __ inhibitors like Phenelzine (Nardil) and Tranylcypromine (Parnate) are used to treat depression
2. __ inhibitors like Entacapone (**Comt**an) and Tolcapone (Tasmar) enhance the effectiveness of \_\_-\_\_ in treating Parkinson’s disease by preventing breakdown of \_\_
1. MAO
2. COMT inhibitors (inhibits enzyme Catechol-O-MethylTransferase) | L-DOPA | DOPA
70
Catecholamines belong to a wider group of transmitters called either *\_\_* or *Biogenic Amines*.
*Monoamines* or *\_\_ \_\_*
71
\_\_ __ damage can lead to a form of chronic pain called __ pain
Nerve tissue | Neuropathic
72
Neuron firing patterns (2 modes) also influences catecholamine release
* __ \_\_ mode: action potentials generated at irregular intervals resulting in __ release of DA.
* __ mode: trains of 2 to 20 spikes at a higher frequency result in __ release of DA and causing extracellular level of DA to be high because its release occurrs faster than it can be cleared and/or metabolized.
1. Single-Spiking | Tonic 4-5 Hz
2. Burst (2-10) | Phasic ~20 Hz
73
Noradrenergic System has Central and PNS components
Central
* Cell bodies in the Brainstem (\_\_ __ and \_\_)
* Their ascending fibers go to Forebrain Structures.
Peripheral: part of the S*ympathetic Nervous System*
* NE neuron fibers extend to target __ throughout the body
* Locus Coeruleus and Medulla
* Forebrain Structures
* Organs
74
The central *Noradrenergic System* is involved in many behavioral functions. Of special interest are 3 things:
1. Arousal
2. Cognition
3. Consolidation of memories of emotional experiences
75
1. Catecholamine Release leads to __ \_\_
2. In lab animals, increased __ \_\_ occurs. At higher doses, this is replaced by __ behaviours (sniffing, head and limb movements, licking and biting)
3. This continuum of behaviour stems from increasing stimulation of DA receptors in the __ \_\_ and \_\_
1. Behavioral Activation
2. Locomotor Activity | Stereotyped
3. Nucleus Accumbens and Striatum
76
Reduced by treatment with agonists at the 5-HT1A, 5-HT1B, and 5-HT2C receptor subtypes. Exacerbated by 5-HT2A and 5-HT4 agonists
Pain
77
1. There are large numbers of \_\_-\_\_ Receptors in the Cortex. They activate the __ \_\_-\_\_ __ (just like α1-receptors)
2. This system increases Ca2+ levels in postsynaptic cells and also activates __ \_\_ \_\_
1. 5-HT2A | PhosphoInositide Second-Messenger System
2. Protein Kinase C (PKC)
78
A family of minority acidic phospholipids in cell membranes. Their principal role is instructional: they interact with proteins
PhosphoInositides
79
Catecholamine Synthesis can be increased by administering __ such as __ or __ \_\_, which has been used to treat __ \_\_
Precursors | Tyrosine | L-DOPA | Parkinson’s Disease
80
1. Almost all Serotonergic Neurons in CNS found along the __ \_\_ __ associated with the __ \_\_
2. The Dorsal and Median __ \_\_ give rise to most of the Serotonergic Fibers in the \_\_
1. midline of Brainstem | Raphe Nuclei
2. Raphe Nuclei Forebrain
\_\_\_\_
(image - Tonic Firing Patterns)
81
TH (Tyrosine Hydroxylase) is the __ \_\_ Enzyme in the pathway. It determines the overall rate of DA or NE synthesis.
Rate-Limiting
82
Reboxetine
Antidepressant
83
1. 5-HT plays a role in processing of pain signals at the level of the spinal cord
2. The complex role involves several __ \_\_ that together produce either __ or __ modulation
1. 5-HT
2. Receptor Subtypes | Inhibitory | Excitatory
84
\_\_ __ \_\_ and __ help us understand which behaviours are under the control of a particular receptor subtype
SKF 38393 is an *Agonist for D1 receptors*; *Quinpirole* activates __ and __ receptors (stimulating hyperactivity)
Receptor Selective Agonists | Antagonists
D2 | D3 Receptors | Hyperactivity
85
VMAT can be blocked by the drug \_\_
Reserpine
86
\_\_ for hypertension blocks storage of \_\_, \_\_, and \_-\_\_ in vesicles
Reserpine | DA | NE | 5-HT
87
* Most common behavioural effect of eliminating brain 5-HT is a large increase in __ \_\_, usually measured by the \_\_-\_\_ \_\_
* Injection of 5-HTP with *Carbidopa*, an AADC *inhibitor* that doesn’t cross the blood–brain barrier, reverses the effect because it __ \_\_ __ of 5-HTP to 5-HT
* 5-HT knockout mice are __ \_\_ __ and attack more times
* If given 5-HTP and Carbidopa they are __ \_\_ __ and __ \_\_ \_\_
* Aggressive Behaviour | Resident-Intruder Test
* Blocks Peripheral Conversion
* Quicker to Attack | Attack More Times
* Slower to Attack | Attack Fewer Times
88
1. During Reuptake of Catecholamines __ and __ move from the synaptic cleft into the nerve terminal via specific __ \_\_ \_\_
2. The molecules are then __ into vesicles or __ \_\_
3. __ \_\_ Uptake plays a vital role in the normal regulation of catecholamine activity
4. Mice with no __ \_\_ do not respond to psychostimulants like cocaine and amphetamine
5. Mutant mice with no __ \_\_ have increased sensitivity to psychostimulants
1. DA | NE | Membrane Transporter Proteins
2. Repackaged or Broken Down
3. Transporter-Mediated
4. DA transporters
5. NE transporters
89
The Reward-Mediating pathway includes input to the VTA from the __ \_\_ (LDT) and Dopaminergic Output from the VTA to the __ \_\_ (NAc)
LateroDorsal Tegmentum | Nucleus Accumbens
90
Some personality disorders are associated with violent behaviours; drugs that can quell such behaviors are called \_\_
SSRIs have been tested because of their ability to enhance __ \_\_
• E.g., fluoxetine (Prozac)
Serenics | Serotonergic Transmission
91
* Breakdown of 5-HT is catalyzed by MAO-A to yield 5-\_ _ \_ _ (HIAA)
* Levels of 5-HIAA in the brain or CSF sre used as a measure of the activity of __ \_\_
MAO-A 5-HydroxyIndoleAcetic Acid (5-HIAA) | Serotonergic Neurons
92
Proposes that low CNS Serotonergic activity is associated with hyperaggressiveness
Serotonin Deficiency Hypothesis of Aggression
93
* After release 5-HT is rapidly removed from synaptic cleft via reuptake by the \_\_-\_\_ \_\_, or \_\_
* These transporters are blocked by __ \_\_ __ \_\_ such as *Fluoxetine* (Prozac)
* Cocaine and MDMA also block SERT, but are not selective. They also affect __ transporters
5-HT transporter | SERT
Selective Serotonin Reuptake Inhibitors (SSRIs)
Cocaine | MDMA | DA
94
Enterochromaffin Cell 5-HT is released onto sensory nerve endings in the gut wall, after which it is cleared from the extracellular space by \_\_
When food is ingested, 5-HT promotes gut __ and __ \_\_
SERT
Peristalsis | Secretory Activity
95
1. __ enhance the opening voltage-gated K+ channels, which shortens the duration of __ \_\_ and reduces Ca2+ influx, and thus \_\_
2. __ \_\_ inhibit neurotransmitter release indirectly by reducing the rate of firing of the cell
1. Autoreceptors | Action Potentials | Exocytosis
2. Somatodendritic Autoreceptors
96
NE can reach an organ such as the heart in two ways:
1. It can be released from __ \_\_ __ at synapse-like contacts with Cardiac cells.
2. It can be released from the __ \_\_ and travel in the bloodstream to the heart (but cannot cross the \_\_-\_\_ \_\_)
1. Sympathetic Noradrenergic Neurons
2. Adrenal Glands | Blood Brain Barrier
97
Neurons can regulate __ of neurotransmitters and control the amount available for release.
Drugs can also be used to promote or block it (e.g., administering __ \_\_)
Synthesis | Transmitter Precursors
98
TH can be phosphorylated by all of the second-messenger-associated Kinases from Chapter 3, including \_\_, \_\_, \_\_, and \_\_/\_\_ __ \_\_. It can also be phosphorylated by kinases of the MAP (Mitogen-Activated Proten) Kinase system including ERK (extracellular signal-related Kinase)
A, G, C, and Calcium/Calmodulin Kinase II
99
Serotonin is synthesized from the amino acid _____ in two steps
1. Tryptophan Hydroxylase converts Tryptophan to \_\_-\_\_
2. __ \_\_ __ \_\_ converts 5-HTP to 5-HT (serotonin)
Tryptophan
1. 5-HydroxyTryptoPhan (5-HTP)
2. Aromatic Amino Acid Decarboxylase (AADC)
100
A low-protein, high-carbohydrate meal will increase ratio of __ to competing Large Neutral Amino Acids (LNAA), allowing more __ to cross the \_\_–\_\_ __ and more \_\_-\_\_ to be made
Tryptophan | Tryptophan | Blood–Brain Barrier | 5-HT
101
Ratio of Tryptophan to other amino acid competitors for transport across blood–brain barrier determines whether __ \_\_ is stimulated or not
Serotonin Synthesis
102
Tryptophan hydroxylase is found only in __ \_\_
Serotonergic Neurons
103
Conversion of Tryptophan to 5-HTP is the __ \_\_ \_\_
Rate-Limiting Step
104
There are two forms of the Tryptophan Hydroxylase gene
* TPH2 is expressed by __ \_\_
* TPH1 is expressed by 5-HT-secreting cells in the __ and __ secreting cells in the __ \_\_
Serotonergic Neurons
Gut | Melatonin | Pineal Gland
105
Catecholamine synthesis begins with the amino acid \_\_
Tyrosine
106
\_\_ __ and __ \_\_ __ \_\_ are found in neurons that make Dopamine (first 2 enzymes in catecholamine syntesis)
Tyrosine Hydroxylase | Aromatic Amino Acid deCarboxylase
107
After synthesis, catecholamines are packaged into
Vesicles
108
A specific transporter in the __ \_\_ membrane known as the __ \_\_ __ recognizes monoamines
Vesicle Membrane | **V**esicular **M**ono**A**mine **T**ransporter (VMAT)
109
Serotonin is transported into vesicles by __ (\_\_ __ \_\_)
VMAT2 (Vesicular Monoamine Transporter)
110
VMAT 1 is found in the __ \_\_
VMAT 2 is present in the \_\_
Both are blocked by \_\_\_\_\_\_
Adrenal Medula
Brain
Reserpine
111
A widespread mode of intercellular communication that occurs in the extracellular fluid (ECF) and in the cerebrospinal fluid (CSF) of the brain with signals moving from source to target cells via energy gradients leading to diffusion and convection (flow)
Volume transmission
112
Some VTA Dopaminergic Neurons are activated by stressful or aversive stimuli
* It appears that __ and __ stimuli activate different subsets of VTA neurons
These subsets are also differentiated by both their inputs and their outputs:
* The \_\_-\_\_ pathway includes input to the VTA from the *LateroDorsal* *Tegmentum* (LDT) and dopaminergic output from the VTA to the *Nucleus* *Accumbens* (NAc)
* The \_\_-\_\_ pathway includes input to the VTA from the *Lateral* *Habenula* (LHb) and dopaminergic output from the VTA to the *Medial* *Prefrontal* *Cortex* (mPFC)
* Rewarding | Aversive
* Reward-Mediating (*LateroDorsal* *Tegmentum to Nucleus* *Accumbens)*
* Aversion-Mediating (*Lateral Habenula to* *Medial* *Prefrontal* *Corte)*
113
1. Withdrawal from opioids activates the __ System, one factor leading to withdrawal symptoms
2. __ \_\_ such as *Clonidine* are often used to treat the symptoms
3. Yohimbine blocks the __ and thus increases __ \_\_ __ and NE release. It was found to provoke __ \_\_ and __ \_\_ in opioid-dependent patients
1. Noradrenergic System
2. α2-Agonists
3. Autoreceptors | Noradrenergic Cell Firing | Withdrawal Symptoms | Drug Craving
114
\_\_-\_\_-\_\_-\_\_ (AMPT) blocks TH, preventing overall __ \_\_ and causing general depletion of these neurotransmitters
α-Methyl-Para-Tyrosine | Catecholamine Synthesis
