CH 6

Question 1

Almost all serotonergic neurons in the CNS are found along the ____ of the brainstem, associated with the ____ ____. The dorsal and _____ raphe nuclei give rise to most of the serotonergic fibers in the forebrain. 5-HT innervation of the forebrain is ____ than that of DA, comparable to ____. 5-HT producing cells also exist in the ____, thus drugs that interfere with 5-HT transmission may also have _____ effects

Answer 1

midline, raphe nuclei, median, greater, NE, gut, peripheral

Question 2

5-HT’s molecular type is an ______.

Answer 2

Indolamine

Question 3

The amino acid that is a precursor to 5-HTP and 5-HT

Answer 3

tryptophan

Question 4

the enzyme that converts tryptophan to 5-hydroxyl-tryptophan (5-HTP); slow

Answer 4

tryptophan hydroxylase

Question 5

the enzyme that converts 5-HTP to 5-HT

Answer 5

aromatic amino acid decarboxylase (AADC)

Question 6

a drug that blocks 5-HT synthesis by irreversibly inhibiting tryptophan hydroxylase

Answer 6

parachlorophenylalanine (PCPA)

Question 7

5-HT synthesis can be stimulated with large doses of ___ or ___. Tryptophan competes with other large, neutral ___ ___ for transport across the ____. The ____ of tryptophan to other aa’s determines the amount of 5-HT in made in the _______. A high carbohydrate diet which stimulates _____ release, can take aa’s out of the ______ and turn them into _______, with the exception of ______. This results in an increase in ______

Answer 7

tryptophan, 5-HTP, amino acids, BBB, ratio, brain, insulin, bloodstream, proteins, tryptophan, 5-HT

Question 8

temporary reductions in 5-HT levels can be achieved in humans by giving an ____ _____ ______ (all aa’s minus tryptophan). Large, aa’s inhibit entry of the remaining tryptophan into the brain. It also stimulates ____ _____ in the liver, which further reduces level of _____ tryptophan, resulting in lower 5-HT ______ in CSF. Reducing 5-HT in this manner can cause ______ of symptoms in previously depressed patients but not ____ ones, and behavioural changes such as increased _____ in healthy subjects

Answer 8

amino acid cocktail, protein synthesis, plasma, metabolites, reappearance, healthy, impulsivity

Question 9

5-HT is packaged by _____ like catecholamines and is thus sensitive to ______.

Answer 9

VMAT2, reserpine

Question 10

The 5-HT transporter than removes 5-HT from the synapse via reuptake

Answer 10

SERT

Question 11

the enzyme that breaksdown 5-HT into 5-HIAA

Answer 11

MAO

Question 12

The metabolite of 5-HT that can be used as a measure for the activity of 5-HT neurons

Answer 12

5-HIAA

Question 13

a drug that acts like amphetamine; reverses monoamine transporters to shoot 5-HT out into the synapse; was prescribed for appetite suppression in obese patients but caused cardiovascular side effects

Answer 13

fenfluramine

Question 14

A recreational drug that acts on SERT with higher affinity than DAT and NET; can cause enhanced sensations and may be used as a therapeutic agent for PTSD

Answer 14

3,4-methylenedioxymethamphetamine (MDMA, ecstasy, molly)

Question 15

drug that blocks SERT and thus acts as an SSRI

Answer 15

fluoxtine (prozac)

Question 16

There are at least ____ different 5-HT receptors, and nearly all are ______. There are ___ main families. Many drugs are relatively _____. The 5-HT1 family has at least ___ subtypes while the _____ family has at least 3 subtypes. Our understanding of them are _______.

Answer 16

14, metabotropic, 7, nonselective, 5, 5-HT2, limited

Question 17

The 5-HT1A receptor is concentrated postsynaptically in the ______, _____ and ______. They are somatodendritic autoreceptors in the ______. These receptors inhibit _____ and/or increase opening or _____ channels to hyperpolarize the cell

Answer 17

hippocampus, amygdala, septum, raphe, cAMP, K+

Question 18

full agonist of 5-HT1A

Answer 18

6-OH-DPAT

Question 19

partial agonist of 5-HT1A

Answer 19

buspirone

Question 20

Systemic administration of 5-HT1A agonists stimulates ______ receptors, but also ______ 5-HT release because all other serotonin receptors get less activation

Answer 20

postsynaptic, reduce

Question 21

a 5-HT1A receptor antagonist

Answer 21

WAY-100635

Question 22

5-HT1B and D receptors serve as _____ ____ on 5-HT terminals that _____ the cell. They also reside postsynaptically in the _____ and ______.

Answer 22

presynaptic autoreceptors, hyperpolarize, striatum, NAcc

Question 23

5-HT2A receptors are distributed widely in the ____ and the _____/_____. They are primarily _____ and activate the _____ 2nd messenger system, resulting in increases in Ca2+ in the postsynaptic cells and activating _______ _____ ____. The hallucinogenic effects of ____ are believed to stem from its ability to stimulate 5-HT2A receptors

Answer 23

cortex, striatum, NAcc, postsynaptic, phosphoinositide, protein kinase C, LSD

Question 24

a 5-HT2A agonist that is hallucinogenic and disrupts 5-HT’s natural filter in the visual cortex

Answer 24

DOI

Question 25

5-HT2A antagonist

Answer 25

ketanserin

Question 26

5-HT2C receptor is a _____ receptor that is promotes the ____ function as the 5-HT2A receptors

Answer 26

postsynaptic, opposite

Question 27

5-HT serves to _____ certain patterns of behaviour. However it is not completely necessary for _____.

Answer 27

suppress, survival

Question 28

to investigate 5-HT function in humans, we can compare the CSF levels of ____ or _____ in the postmortem brain regions with behavioural traits or ______ disorders, assess responses to _____ or receptor ____/_____, identify associations between psychiatric disorders and _____ _____ or ____ and _____ receptors

Answer 28

5-HIAA, 5-HT, neuropsychiatric, SSRIs, agonists/antagonists, genetic polymorphisms, SERT, 5-HT

Question 29

In animals, we can also ____ 5-HT neurons with selective neurotoxins such as ______, genetic engineer mice lacking certain 5-HT _______, delete _____ which produces 5-HT, and run additional psychopharmacological studies

Answer 29

lesion, 5,7-DHT, receptors, Thp2

Question 30

Some functions 5-HT has been implicated in include

Answer 30

1. sensory filtering, 2. temperature regulation, 3. sleep/wake cycles, 4. pain modulation, 5. learning and memory, 6. cognitive flexibility

Question 31

SSRIs or other 5-HT releasers such as _____ or _____ receptor agonists, reduce food intake by reducing the _____ of food consumed per meal (but not the ____ of meals), and shifting food preference away from _____ food. 5-HT _____ neurons in the paraventricular _______, which signal short term ______. _____ receptor agonists, stimulate somatodendritic autoreceptors, reducing 5-HT release and leading to ______.

Answer 31

5-HT1B, 5-HT2C, amount, number, fatty, disinhibits, hypothalamus, satiety, 5-HT1A, hyperphagia

Question 32

5-HT1A _____ reduce anxiety, whereas 5-HT1A _____ mice show increased anxiety. Drugs that target this receptor are used to treat _____ disorders.

Answer 32

agonists, KO, anxiety

Question 33

effects of 5-HT1A agonists on reducing anxiety are likely due to _____ effects because ______ stimulation/inhibition of 5-HT terminals in stress-related brain regions (____) reduce/increase open arm time in the _____ _____ ____ via 5-HT1A mediated mechanisms. In other words, stimulation of these receptors caused ____ in anxiety, while inhibition caused ______ in anxiety. Activation of other postsynaptic 5-HT receptors ______ anxiety like behaviour, and _____ or 2C KO mice showed reduced anxiety.

Answer 33

postsynaptic, optogenetic, BNST, elevated plus maze, reduction, increase, increase, 5-HT2A

Question 34

behaviours meant to cause physical/psychological harm to a victim

Answer 34

aggression

Question 35

____ 5-HT activity is associated with increased aggressive behaviour. However, this can depend on the ____ background, drug treatment _____ and ___ of aggression. _____ agonists reduce aggression in mice, and this may be due to actions on _______ receptors rather than reduced 5-HT release.

Answer 35

low, genetic, regimen, type, 5-HT1A/B, postsynaptic

Question 36

In the resident _____ paradigm with mice, mice overexpressing the _____ _______ in the raphe showed ______ aggression.

Answer 36

intruder, 5-HT1A, autoreceptors, hyper

Question 37

the ____ _____, _____, ____ and _____ mediate aggression and all express the 5-HT1A/B postsynaptic receptors and receive 5-HT inputs

Answer 37

cerebral cortex, hypothalamus, amygdala, striatum,

Question 38

acute tryptophan depletion in healthy subjects can ____ aggressive behaviour in laboratory tests, resulting in more ____ by the subject against the opponent.

Answer 38

increase, attacks

Question 39

increased aggression may be related to 5-HT regulation of

Answer 39

impulsivity

Question 40

acting without adequate forethought, predisposition toward rapid, unplanned reactions without regard to their negative consequences

Answer 40

impulsivity

Question 41

rat performs an attention task (a light flashes briefly in a certain location, rat must nosepoke it quickly to get reward)

Answer 41

5 choice serial reaction time task

Question 42

5-HT is particularly important for mediating _____, and may act as a ____ to control impulsive responses.

Answer 42

waiting, brake

Question 43

5-HT selective lesions with _____ impair waiting by increasing ____ _____. 5-HT2C ____ also can impair impulsivity. 5-HT2C ____ reduce impulsive action. This has important implications for ___ ___, and _____

Answer 43

5,7-DHT, premature responses, antagonists, agonists, drug addictions, ADHD