Term
| DA, EPI, and NE are all considered |
|
Definition
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|
Term
| The synthesis of catecholamine NTs begins with... |
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Definition
|
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Term
|
Definition
| Tyrosine is obtained through the diet |
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|
Term
| Neurons that use DA contain what 2 enzymes? |
|
Definition
tyrosine hydroxylase (TH)
aromatic amino acid decarboxylase (AADC) |
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|
Term
| Neurons that use NE possess what enzymes? |
|
Definition
tyrosine hydroxylase (TH)
aromatic amino acid decarboxylase (AADC)
dopamine beta-hydroxylase (DBH) |
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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 |
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Term
| What controls TH (tyrosine hydroxylase) activity? |
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Definition
| Concentration of DA and NE (high concentrations inhibits TH - negative feedback) and neuronal firing (increased firing stimulates TH activity) |
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Term
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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) |
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Term
| Where is the rate of classical NT (DA, NE, ACh, 5-HT) synthesis greatest? |
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Definition
| At the nerve terminal, near the site of transmitter release |
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Term
| What transports catecholamines into vesicles in the presynaptic terminal and what blocks this protein? |
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Definition
Vesicular monoamine transporter proteins (VMAT2...VMAT1 is in the adrenal medulla)
it is blocked by reserpine |
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Term
| What are the effects of resperine (chemically and behaviorally)? |
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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 |
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Term
| Two psychostimulants that cause a release of catecholamines independently of nerve cell firing |
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Definition
| amphetamine and methamphetamine cause the release of catecholamines without nerve cell firing |
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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 |
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Definition
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Term
How do terminal autoreceptors of catecholamines work?
How do somatodendritic autoreceptors work? |
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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 |
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Term
| The subtypes of DA and NE autoreceptors |
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Definition
DA autoreceptors are of the D2 subtype
NE autoreceptors are of the alpha2 subtype |
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Term
| What is Clonidine used for and what does it do? |
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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) |
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Term
| What is Yohimbine and what does it do? |
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Definition
| Yohimbine is an alpha2 antagonist...so it increases noradrenergic activity and induces withdrawal symptoms and increased drug craving in opioid-dependent patients |
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Term
| True/False: deletion of the DA transporter gene causes typical behavioral activation in response to psychostimulants like cocaine or amphetamine |
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Definition
| FALSE...deletion of the DA transporter gene does NOT show the typical behavioral activation in response to psychostimulants like cocaine or amphetamine |
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Term
| What does the genetic deletion of the NE reuptake transporter gene cause (behaviorally)? |
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Definition
| Genetic deletion of the NE transporter gene causes increased sensitivity to psychostimulants like cocaine or amphetamines |
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Term
Actions of tricyclic antidepressants.
How does Reboxetine work? |
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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. |
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Term
| Chemical effects of cocaine |
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Definition
| Cocaine blocks the reuptake of DA, NE, and 5-HT |
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Term
| The primary enzymes that break down catecholamines: |
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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) |
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|
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 |
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|
Term
| HVA, MHPG, and VMA are excreted via |
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Definition
| HVA, MHPG, and VMA are excreted via the urine |
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Term
| Phenelzine and tranylcypromine are what kind of drug |
|
Definition
| Phenelzine and tranylcypromine are both MAO inhibitors (antidepressants...block the metabolism of catecholamines) |
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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 |
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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 |
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Term
| What are the major catecholamines in the brain |
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Definition
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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... |
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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) |
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|
Term
| Dopaminergic axons originating from the VTA project to... |
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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 |
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Term
| The tuberohypophyseal DA pathway (originating in the hypothalamus) is important in controlling... |
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Definition
| The tuberohypophyseal DA pathway is important in controlling the secretion of the hormone prolactin by the pituitary gland |
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|
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 |
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|
Term
| How does 6-OHDA (6-hydroxydopamine) work? |
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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? |
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Definition
| Activation of D2 receptors by DA from the hypothalamus inhibits prolactin secretion...blockade of D2 receptors stimulates prolactin release |
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Term
| D1 vs. D2 effects on adenylyl cyclase |
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Definition
| Activation of D1 receptors stimulate adenylyl cyclase (Gs protein) while activation of D2 receptors inhibits adenylyl cyclase (Gi protein) |
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Term
| In some cells, the functions of D2 receptors are to inhibit adenylyl cyclase and... |
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Definition
| enhance K+ channel opening |
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|
Term
What is Apomorphine?
Apomorphine causes behavioral activation similar to those seen with... |
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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. |
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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 |
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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) |
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|
Term
| The therapeutic benefit anti-schizophrenic drugs comes from... |
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Definition
| the blocking of DA receptors (D2) in the limbic system or the cortex (though these drugs can cause troublesome motor side effects) |
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Term
| Describe the behavioral supersensitivity syndrome of rats given haloperidol chronically |
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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 |
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Term
| How are haloperidol and 6-OHDA similar and different? |
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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 |
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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 |
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|
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) |
|
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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 |
|
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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 |
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Term
| Adrenoceptors mediate both NT (mainly __) and hormonal (mainly __) actions |
|
Definition
| Adrenoceptors mediate both NT (mainly NE) and hormonal (mainly EPI) actions |
|
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Term
| The 2 adrenoceptor subtypes |
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Definition
| alpha and beta adrenoceptors |
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Term
| Where are alpha2 adreno-autoreceptors found and what do they do? |
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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 |
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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) |
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Term
| The sedative and anxiolytic effects of dexmedetomidine (Precedex) are believed to be mediated by... |
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Definition
| alpha2-autoreceptors in the LC |
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Term
| NE-mediated arousal involves what receptors? |
|
Definition
| NE-mediated arousal involves alpha1 and beta adrenoceptors |
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Term
| The eating response caused by NE being injected into the paraventricular nucleus (PVN) appears to be due to activation of... |
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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) |
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Term
| What subtype of beta adrenoceptors are found in the airways (respiratory system) and which subtype is found in the heart? |
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Definition
| Beta2 adrenoceptors are found in the respiratory system and beta1 adrenoceptors are found in the heart |
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Term
| Asthma is more commonly treated with a selective...such as albuterol |
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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 |
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|
Term
Drug treatments of hypertension (high blood tension) involve the stimulation of...
How does this alleviate hypertension? side effects? |
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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 |
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|
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) |
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|
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
|
|
Term
|
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
|
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
|
|
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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