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Psych 436 - Final
Catecholamines: Systems and Receptors (Ch5, L15)
91
Psychology
Undergraduate 4
11/29/2008

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Term
DA, EPI, and NE are all considered
Definition
catecholamines
Term
The synthesis of catecholamine NTs begins with...
Definition
the amino acid, tyrosine
Term
How is tyrosine obtained
Definition
Tyrosine is obtained through the diet
Term
Neurons that use DA contain what 2 enzymes?
Definition
tyrosine hydroxylase (TH)
aromatic amino acid decarboxylase (AADC)
Term
Neurons that use NE possess what enzymes?
Definition
tyrosine hydroxylase (TH)
aromatic amino acid decarboxylase (AADC)
dopamine beta-hydroxylase (DBH)
Term
What is the rate-limiting enzyme in the catecholamine synthesis pathway?
Definition
tyrosine hydroxylase (TH)
conversion of tyrosine to DOPA is the slowest step
Term
What controls TH (tyrosine hydroxylase) activity?
Definition
Concentration of DA and NE (high concentrations inhibits TH - negative feedback) and neuronal firing (increased firing stimulates TH activity)
Term
What is AMPT?
Definition
AMPT= alpha-methyl-para-tyrosine...a drug that inhibits TH (tyrosine hydroxylase) and therefore prevents catecholamine synthesis causing return of depressive symptoms in patients previously using anti-depressants (showing patients' recovery is based on adequate catecholamine levels in the brain)
Term
Where is the rate of classical NT (DA, NE, ACh, 5-HT) synthesis greatest?
Definition
At the nerve terminal, near the site of transmitter release
Term
What transports catecholamines into vesicles in the presynaptic terminal and what blocks this protein?
Definition
Vesicular monoamine transporter proteins (VMAT2...VMAT1 is in the adrenal medulla)
it is blocked by reserpine
Term
What are the effects of resperine (chemically and behaviorally)?
Definition
Resperine blocks VMAT (vesicular monoamine transporters) which causes DA and NE levels to decline (no longer protected by vesicle from breakdown by enzymes in the nerve terminal)...causes sedation in animals and depression in humans
Term
Two psychostimulants that cause a release of catecholamines independently of nerve cell firing
Definition
amphetamine and methamphetamine cause the release of catecholamines without nerve cell firing
Term
Repeated, relatively invariant behaviors associated with a particular situation or drug treatment...often occur following a high dose of psychostimulant such as cocaine or amphetamine
Definition
stereotyped behaviors
Term
How do terminal autoreceptors of catecholamines work?
How do somatodendritic autoreceptors work?
Definition
Terminal autoreceptors inhibit catecholamine release by reducing the amount of Ca2+ that enters the terminal (less Ca2+, less synaptic vesicle/membrane fusion)
Somatodendritic autoreceptors inhibit release indirectly by reducing the rate of firing of the cell
Term
The subtypes of DA and NE autoreceptors
Definition
DA autoreceptors are of the D2 subtype
NE autoreceptors are of the alpha2 subtype
Term
What is Clonidine used for and what does it do?
Definition
Clonidine is an alpha2 agonist used to treat symptoms of opioid withdrawal by stimulating the autoreceptors and inhibit noradrenergic cell firing (withdrawal symptoms like diarrhea, and increased heart rate and blood pressure due to activation of the noradrenergic system)
Term
What is Yohimbine and what does it do?
Definition
Yohimbine is an alpha2 antagonist...so it increases noradrenergic activity and induces withdrawal symptoms and increased drug craving in opioid-dependent patients
Term
True/False: deletion of the DA transporter gene causes typical behavioral activation in response to psychostimulants like cocaine or amphetamine
Definition
FALSE...deletion of the DA transporter gene does NOT show the typical behavioral activation in response to psychostimulants like cocaine or amphetamine
Term
What does the genetic deletion of the NE reuptake transporter gene cause (behaviorally)?
Definition
Genetic deletion of the NE transporter gene causes increased sensitivity to psychostimulants like cocaine or amphetamines
Term
Actions of tricyclic antidepressants.
How does Reboxetine work?
Definition
Tricyclic antidepressants inhibit the reuptake of NE and non-catecholamine transmitter 5-HT)
Reboxetine selectively inhibits NE reuptake by blocking only the NE transporter.
Term
Chemical effects of cocaine
Definition
Cocaine blocks the reuptake of DA, NE, and 5-HT
Term
The primary enzymes that break down catecholamines:
Definition
catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) which includes MAO-A and MAO-B
Term
The major metabolite of DA
The major metabolites of NE
Definition
Major metabolite of DA= homovanillic acid (HVA)
Major metabolites of NE= 3-methoxy-4-hydroxy-phenylglycol (MHPG) and vanillymandelic acid (VMA)
Term
Metabolism of NE within the brain primarily leads to...
Definition
Metabolism of NE within the brain primarily leads to MHPG (3-methoxy-4-hydroxy-phenylglycol...VMA (vanillymandelic acid) is a more common metabolite in the periphery
Term
HVA, MHPG, and VMA are excreted via
Definition
HVA, MHPG, and VMA are excreted via the urine
Term
Phenelzine and tranylcypromine are what kind of drug
Definition
Phenelzine and tranylcypromine are both MAO inhibitors (antidepressants...block the metabolism of catecholamines)
Term
COMT inhibitors such as Comtan and Tasmar are therapies for Parkinson's because they...
Definition
inhibit the breakdown of L-DOPA
Term
Describe volume transmission
Definition
Volume transmission is the phenomenon characterized by diffusion of a chemical signal through the extracellular fluid to other synapses, not just the neighboring synapse
Term
What are the major catecholamines in the brain
Definition
DA and NE
Term
Axons of dopaminergic neurons in the substantia nigra ascend to...
Definition
Axons of dopaminergic neurons in the substantia nigra ascend to the caudate-putamen (the striatum)
(the nigrostriatal tract...this tract is severely damaged in Parkinson's patients)
Term
The nigrostriatal DA tract plays a crucial role in...
Definition
The nigrostriatal DA tract plays a crucial role in the control of movement (as seen in Parkinson's patients with severely damaged nigrostriatal tracts)
Term
Dopaminergic axons originating from the VTA project to...
Definition
Dopaminergic axons from the VTA project to the limbic system (nucleus accumbens, septum, amygdala, and hippocampus) ...this is the mesolimbic DA pathway
OR they project to the cerebral cortex, particularly the prefrontal area...this is the Mesocortical DA pathway
Term
The tuberohypophyseal DA pathway (originating in the hypothalamus) is important in controlling...
Definition
The tuberohypophyseal DA pathway is important in controlling the secretion of the hormone prolactin by the pituitary gland
Term
What does 6-hydroxydopamine (6-OHDA) do?
Does it easily cross the BBB?
Definition
6-hydroxydopamine (6-OHDA) lesions catecholamine pathways, particularly those using DA
No, it does not easily cross the BBB so it must be injected directly into the brain
Term
How does 6-OHDA (6-hydroxydopamine) work?
Definition
6-OHDA enters catecholaminergic neurons through DA transporters (its structure is very close to DA) and damages the nerve terminals, sometimes killing the entire cell
Term
True/False: All the DA receptor subtypes are metabotropic
Definition
TRUE: All the DA receptor subtypes are metabotropic
Term
D1 and D2 receptors are found in large numbers in...
Definition
the striatum (major termination site of the nigrostriatal DA pathways) and the nucleus accumbens (major termination siteof the mesolimbic DA pathways)
Term
What effect does the activation of D2 receptors by DA from the hypothalamus and blockade of these receptors have on prolactin?
Definition
Activation of D2 receptors by DA from the hypothalamus inhibits prolactin secretion...blockade of D2 receptors stimulates prolactin release
Term
D1 vs. D2 effects on adenylyl cyclase
Definition
Activation of D1 receptors stimulate adenylyl cyclase (Gs protein) while activation of D2 receptors inhibits adenylyl cyclase (Gi protein)
Term
In some cells, the functions of D2 receptors are to inhibit adenylyl cyclase and...
Definition
enhance K+ channel opening
Term
What is Apomorphine?
Apomorphine causes behavioral activation similar to those seen with...
Definition
Apomorphine is a D1 and D2 agonist now used to treat ED...it causes behavioral activation similar to those seen with amphetamine and cocaine.
Term
D2 antagonists elicit what kind of behavior? What is an example of a D2 antagonist?
Definition
D2 antagonists suppress spontaneous exploratory and locomotor behavior and at high doses it elicits catalepsy (lack of spontaneous movement, even when forced into an uncomfortable position)
Haloperidol is a D2 antagonist
Term
Catalepsy is particularly related to the inhibition of DA receptors in...
Definition
Catalepsy is particularly related to the inhibition of DA receptors in the striatum (the nigrostriatal DA pathway plays an important role in the control of movement)
Term
The therapeutic benefit anti-schizophrenic drugs comes from...
Definition
the blocking of DA receptors (D2) in the limbic system or the cortex (though these drugs can cause troublesome motor side effects)
Term
Describe the behavioral supersensitivity syndrome of rats given haloperidol chronically
Definition
After given haloperidol chronically and then stopped (unblocking of the D2 receptors) and then given a DA agonist (like apomorphine), the rats with respond more strongly than controls not pretreated with haloperidol
Term
How are haloperidol and 6-OHDA similar and different?
Definition
They both reduce the amount of DA stimulation of D2 receptors. Haloperidol does this by blocking the receptors, 6-OHDA causes a long-lasting depletion of DA
Term
Behavioral supersenstivity associated with haloperidol and 6-OHDA pretreatment is thought to be due to...
Definition
up-regulation of D2 receptors on the postsynaptic cell in the striatum
Term
NE-containing neurons within the brain are located...
Definition
NE-containing neurons within the brain are located in the pons and medulla, particularly the locus coeruleus (LC)
Term
True/False: blood-borne NE does not reach the brain b/c it is effectively excluded by the BBB
Definition
TRUE: blood-borne NE does not reach the brain b/c it is effectively excluded by the BBB
Term
These neurons play an important role in vigilance (being alert to important stimuli in the environment)
Definition
Noradrenergic neurons of the LC play an important role in vigilance
Term
Receptors for NE and EPI aka
...and are all ionotropic, metabotropic, or either?
Definition
Receptors for NE and EPI are also called adrenergic receptors or adrenoceptors...they are all metabotropic
Term
Adrenoceptors mediate both NT (mainly __) and hormonal (mainly __) actions
Definition
Adrenoceptors mediate both NT (mainly NE) and hormonal (mainly EPI) actions
Term
The 2 adrenoceptor subtypes
Definition
alpha and beta adrenoceptors
Term
Where are alpha2 adreno-autoreceptors found and what do they do?
Definition
Alpha2 adreno-autoreceptors are found on noradrenergic nerve terminals and on the cell bodies of noradrenergic neurons in the LC...they inhibit noradrenergic cell firing and reduce NE release from terminals
Term
How do beta1, beta2, alpha1, and alpha2 adrenoceptors work?
Definition
Beta1 and Beta2 both stimulate adenylate cyclase and enhance cAMP formation (like D1 receptors).
Alpha1 adrenoceptors increases the concentration of Ca2+ in the postsynaptic cell throug the phosphoinositide 2nd messenger system.
Alpha2 adrenoceptors inhibit adenylyl cyclase (inhibit cAMP production) and increase K+ channel opening (like D2 receptors)
Term
The sedative and anxiolytic effects of dexmedetomidine (Precedex) are believed to be mediated by...
Definition
alpha2-autoreceptors in the LC
Term
NE-mediated arousal involves what receptors?
Definition
NE-mediated arousal involves alpha1 and beta adrenoceptors
Term
The eating response caused by NE being injected into the paraventricular nucleus (PVN) appears to be due to activation of...
Definition
The eating response of caused by NE being injected into the PVN appears to be due to activation of alpha2 receptors (as seen by using alpha2 agonists which cause the same response)
Term
What subtype of beta adrenoceptors are found in the airways (respiratory system) and which subtype is found in the heart?
Definition
Beta2 adrenoceptors are found in the respiratory system and beta1 adrenoceptors are found in the heart
Term
Asthma is more commonly treated with a selective...such as albuterol
Definition
Asthma is more commonly treated with a selective beta adrenoceptor agonist such as albuterol
Term
What effect does stimulation of alpha adrenoceptors have on blood vessels in the bronchial lining?
Definition
Stimulation of alpha adrenoceptors causes constriction of the blood vessels in the bronchial lining
Term
Drug treatments of hypertension (high blood tension) involve the stimulation of...
How does this alleviate hypertension? side effects?
Definition
Drug treatments of hypertension involve alpha2 adrenoceptor agonists...this inhibits the sympathetic nervous system while enhancing the parasympathetic nervous system (to decrease heart rate and blood pressure)...typical side effects are sedation and sleepiness
Term
Prazosin causes a dilation of blood vessels by...
Definition
Prazosin causes a dilation of blood vessels by blocking alpha1 adrenoceptors (Prazosin is an alpha1 adrenoceptor antagonist and used to treat hypertension)
Term
The main function of Propranolol is to...
Definition
The main function of Propranolol is to block the beta adrenoceptors in the heart thereby reducting the heart's contractile force (Propranolol is a beta adrenoceptor antagonist and is used to treat hypertension)
Term
Metopropolol used instead of propranolol because....
Definition
it is a selective beta1 antagonist...beta1 adrenoceptors are the main beta subtype found in the heart...less side effects
Term
What is Phenelzine and what is it used for?
Definition
Phenelzine is an alpha1 agonist used to relieve nasal congestion
Term
What is Clonidine and what is it used for?
Definition
Clonidine is an alpha2 agonist used to treat hypertension and drug withdrawal symptoms
Term
What is Albuterol and what does it do?
Definition
Albuterol is a beta2 agonist used to relieve bronchial congestion (asthma)
Term
What is Yohimbine and what is it used for?
Definition
Yohimbine is an alpha2 antagonist used to treat male impotence
Term
This type of medication is often used to relieve the physiological symptoms brought on my anxiety disorders
Definition
Beta blockers are used to treat the physiological symptoms (such as increased heart rate) in patients with anxiety disorders
Term
DA has dose-dependent effects on peripheral...
Definition
DA has dose-dependent effects on peripheral blood vessels
Term
In monoamine ascending neuromodulatory systems (DA, NE, and 5-HT pathways) a few thousand cells in ________ send broad, diffuse projections to _______
Definition
In all three pathways, a few thousand cells in midbrain nuclei send broad, diffuse projections to large areas of the forebrain
Term
Tyrosine is an amino acid created from.....
Definition
Tyrosine is an amino acid created from phenylalanine in the diet
Term
EPI is formed from _____ by the enzyme _______
Definition
EPI is formed from NE by the enzyme phenylethanolamine N-methyltransferase (PNMT)
Term
In the brain, all monoamines are packaged into vesicles by...
Definition
VMAT2
Term
MAOs are found...
Definition
MAOs are found on the outer membranes of presynaptic mitochondria
Term
COMT (catechol-O-methytransferase) is found...
Definition
COMT (metabolizes catecholamines) is found in the postsynaptic membrane
Term
True/False: Within the synapse, catecholamine metabolism is much faster than uptake
Definition
FALSE...Within the synopse, catecholamine uptake is FASTER than metabolism
Term
The 2 major noradrenergic projections
Definition
1.Dorsal Noradrenergic Bundle (DNAB) originates in the locus coeruleus and innervates the forebrain
2.Ventral Noradrenergic Bundle (VNAB) innervates the bed nuclus of stria terminalis
Term
This structure of the brain helps mediate behavioral responsiveness to stimuli
Definition
the locus coeruleus (LC)
(inverted U-shape graph of performance vs. LC activity)
Term
True/False: The LC stains positive for DBH (dopamine beta-hydroxylase) but negative for PNMT (phenylethanoamine N-methyltransferase)
Definition
TRUE: The LC stains positive for DBH (converts DA->NE) but negative for PNMT (converts NE->EPI)
Term
How are noradrenergic neurons affected by morphine?
Definition
Noradrenergic neurons have mu-opioid receptors and are acutely inhibited by morphine...eventually they ADAPT by increasing their excitability)
Term
Overexcitability of LC neurons contributes to...
Definition
Overexcitability of LC neurons contributes to opiate drug withdrawal (restlessness, irritability)
Term
Overexcitability of the ventra noradrenergic bundle pathway (VNAB) contributes to...
Definition
Overexcitability of VNAB pathway contributes to anxiety/stress
Term
The mesolimbic DA pathway projects from ____ to _____(4)
Definition
The mesolimbic DA pathway projects from the ventral tegmental area (VTA) to the nucleus accumbens, hippocampus, lateral septum, and amygdala
Term
What is bradykinesia?
Definition
slow movement, characteristic of Parkinson's Disease
Term
MPTP is converted by ___ to ___...What is MPTP used for?
Definition
MPTP is converted by MAO-B to MPP+, a potent neurotoxin that induces severe PD.
MPTP is used experimentally to produce DA lesions in primates (Rats are RESISTANT to MPTP)
Term
After taking Reserpine, behavior is restored by taking....
Definition
L-DOPA
Term
6-OHDA is taken up into catecholamine terminals by...
Definition
Dopamine transporter (DAT) and norepinephrine transporter (NERT)
Term
DA-deficient mice are normal until...
Definition
DA-deficient mice are normal until ~10-15 days after birth...they become akinetic but they do eat/drink if you put the food/water directly in front of them (behavior restored by L-DOPA)
Term
Explain the "paradoxical" effect of movement without DA
Definition
If a rat that lacks DA and is almost completely akinetic is placed in a tank of cold water, he will swim normally...akinetic Parkinson's patients will get up during fire alarms (DA is involved in "psychomotor" stimulation)
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