4 - Catecholamines Flashcards
- 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 __
14 | Metabotropic
Hippocampus | Septal | Amygdala | Dorsal
cAMP Synthesis | Adenylyl Cyclase
K+ channels | Hyperpolarization
- 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 __ __
- 5-HT
- 5-HT
- Neuron Firing
- 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
- Vagus Nerve
- 5-HT | Gut | Induces Vomiting
- 5-HT3 Antagonists
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 _ _ _ _
- Experimentally
- Appetite Suppression
- Serotonergic Axons
- PTSD
Adjectival Forms of Catecholamines are (3)
- Dopaminergic
- Noradrenergic
- Adrenergic
The __ __ secretes __ and __ into the bloodstream where they act as hormones
Neurotransmitter function of __ is relatively minor
Adrenal Medulla | Epinephrine | Norepinephrine
Epinephrine
Epinephrine and Norepinephrine are also known as __ and __
Adrenaline and Noradrenaline
- 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)
- Metabotropic | α | β
- cAMP (Cyclic Adenosine Monophosphate)
- α1-receptors | Phosphoinositide Second-Messenger System
- Synthesis of cAMP
Brain areas involved in __ receive substantial Serotonergic __ and express several 5-HT receptor subtypes
Aggression | Innervation (stimulate a nerve; supply energy to)
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 __ __ __
β2 | β1 | Adverse Cardiovascular Effects
Adrenergic Agonists or Antagonists are often used in treatment of non-psychiatric conditions because of the widespread distribution of adrenergic receptors in __ __
Peripheral Organs
Pain felt in response to a stimulus that is not usually painful
Allodynia
Some drugs cause release independently of cell firing, like __ and __, which trigger both __ and __ release
Amphetamine and Methamphetamine | Catecholamine and Serotonin
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)
Generalized Anxiety Disorder | Palpitations | Flushing | Tachycardia
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 __
Antagonists | Hypertension
- __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
- SSRIs
- 1A | 1A
- 1A | Postnatal Development | Anxiety
- 1A | Anxiety Disorders
An agonist that stimulates both D1 and D2 receptors. Causes behavioural activation similar to that seen with stimulants like __ and __
Apomorphine | Cocaine | Amphetamine
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?
Waking | Sleep
Locus Coeruleus | Septal | Preoptic
Spent more time awake
Atomoxetine
ADHD Treatment
Catecholamine release is inhibited by __ on neuron cell bodies, terminals, and dendrites
Autoreceptors
Drugs that stimulate autoreceptors inhibit catecholamine release, but conversely, __ __ enhance rate of release
Autoreceptor Antagonists
The Aversion-Mediating pathway includes input to the VTA from the __ __ (LHb) and Dopaminergic Output from the VTA to the __ __ __ (mPFC)
Lateral Habenula | Medial Prefrontal Cortex
- 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 __ __
Behavioral Supersensitivity
Agonists
Striatum | Up Regulation
The memory-enhancing effects of EPI may be mediated by its ability to increase __ __ __
Blood Glucose Levels
Breakdown Products
Metabolites
Breakdown of Catecholamines by Catechol-O-MethylTransferase (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
- Reserpine administration depletes catecholamines and makes bunnies __
- Adminitering DOPA to bunnies thereafter makes them __
- Lethargic
- Energized
Drugs that stimulate autoreceptors, inhibit __ release
Catecholamine Release
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
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
What are the Catecholamines? (3)
Dopamine (DA)
Norepinephrine / Noradrenaline (NE)
Epinephrine / Adrenaline (EPI)
The second enzyme, AADC, is the same for synthesis of __ and __
Catecholamines | 5-HT
(Aromatic Amino Acid deCarboxylase)
High Levels of __ tend to inhibit TH (negative feedback)
Catecholamine
When neurons are firing at a high rate, such as during stress, TH is stimulated and __ __ accelerates
Catecholamine Synthesis
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
__ and Risperidone (Risperdal) block 5-HT2A receptors and __ __ receptors
Clozapine | D2 Dopamine
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
- Locus Coeruleus also projects to __ __ (PFC), which has roles in cognitive functions like __ and __ __
- Activation of α2-receptors in the PFC using selective agonists, such as Clonidine and Guanfacine, enhances __ __. It helps monkeys to not be fooled by __
- Prefrontal Cortex | Attention | Working Memory
- Working Memory | Distractors
Ctecholamine Synthesis Steps (4)
Thyrosine
DOPA
Dopamine
Norepinephrine
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
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
DA receptor knockout mice:
- D1 receptor knockout mice exhibit behavioral abnormalities and deficits in __ __
- D2 knockout mice show __ __ __
- Mice with D1 and D2 double knockouts __
- Cognitive Tasks
- Impaired Movement | Coordination | Posture Control
- Die in the second or third week of life
- DA uses five receptor subtypes __ to __
- All are __. They interact with G proteins and function via __ __
- __ and __are similar (D1-like receptors)
- __ __ and __ are a separate family (D2-like receptors)
- D1 to D5
- Metabotropic | Second Messengers
- D1 | D5
- D2 | D3 | D4
Dopaminergic System originates in several cell groups, mostly in the brainstem. Classification system for DA and NE neurons:
- Cell groups A1 to A7 are __
- Cell groups A8 to A16 are __
- Noradrenergic
- Dopaminergic
Ascending Dopaminergic (DA) system is divided into three pathways
- The __ __ axons from the A9 cell group in the __ __ extend to the __ or __-__
- 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
- Nigrostriatal Tract | Substantia Nigra | Striatum (Caudate-Putamen)
- Ventral Tegmental Area | Mesolimbic Dopamine | Mesocortical Dopamine