CH 6 Flashcards
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
midline, raphe nuclei, median, greater, NE, gut, peripheral
5-HT’s molecular type is an ______.
Indolamine
The amino acid that is a precursor to 5-HTP and 5-HT
tryptophan
the enzyme that converts tryptophan to 5-hydroxyl-tryptophan (5-HTP); slow
tryptophan hydroxylase
the enzyme that converts 5-HTP to 5-HT
aromatic amino acid decarboxylase (AADC)
a drug that blocks 5-HT synthesis by irreversibly inhibiting tryptophan hydroxylase
parachlorophenylalanine (PCPA)
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 ______
tryptophan, 5-HTP, amino acids, BBB, ratio, brain, insulin, bloodstream, proteins, tryptophan, 5-HT
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
amino acid cocktail, protein synthesis, plasma, metabolites, reappearance, healthy, impulsivity
5-HT is packaged by _____ like catecholamines and is thus sensitive to ______.
VMAT2, reserpine
The 5-HT transporter than removes 5-HT from the synapse via reuptake
SERT
the enzyme that breaksdown 5-HT into 5-HIAA
MAO
The metabolite of 5-HT that can be used as a measure for the activity of 5-HT neurons
5-HIAA
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
fenfluramine
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
3,4-methylenedioxymethamphetamine (MDMA, ecstasy, molly)
drug that blocks SERT and thus acts as an SSRI
fluoxtine (prozac)
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 _______.
14, metabotropic, 7, nonselective, 5, 5-HT2, limited
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
hippocampus, amygdala, septum, raphe, cAMP, K+
full agonist of 5-HT1A
6-OH-DPAT
partial agonist of 5-HT1A
buspirone
Systemic administration of 5-HT1A agonists stimulates ______ receptors, but also ______ 5-HT release because all other serotonin receptors get less activation
postsynaptic, reduce
a 5-HT1A receptor antagonist
WAY-100635
5-HT1B and D receptors serve as _____ ____ on 5-HT terminals that _____ the cell. They also reside postsynaptically in the _____ and ______.
presynaptic autoreceptors, hyperpolarize, striatum, NAcc
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
cortex, striatum, NAcc, postsynaptic, phosphoinositide, protein kinase C, LSD
a 5-HT2A agonist that is hallucinogenic and disrupts 5-HT’s natural filter in the visual cortex
DOI
5-HT2A antagonist
ketanserin
5-HT2C receptor is a _____ receptor that is promotes the ____ function as the 5-HT2A receptors
postsynaptic, opposite
5-HT serves to _____ certain patterns of behaviour. However it is not completely necessary for _____.
suppress, survival
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
5-HIAA, 5-HT, neuropsychiatric, SSRIs, agonists/antagonists, genetic polymorphisms, SERT, 5-HT
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
lesion, 5,7-DHT, receptors, Thp2
Some functions 5-HT has been implicated in include
- sensory filtering, 2. temperature regulation, 3. sleep/wake cycles, 4. pain modulation, 5. learning and memory, 6. cognitive flexibility
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 ______.
5-HT1B, 5-HT2C, amount, number, fatty, disinhibits, hypothalamus, satiety, 5-HT1A, hyperphagia
5-HT1A _____ reduce anxiety, whereas 5-HT1A _____ mice show increased anxiety. Drugs that target this receptor are used to treat _____ disorders.
agonists, KO, anxiety
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.
postsynaptic, optogenetic, BNST, elevated plus maze, reduction, increase, increase, 5-HT2A
behaviours meant to cause physical/psychological harm to a victim
aggression
____ 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.
low, genetic, regimen, type, 5-HT1A/B, postsynaptic
In the resident _____ paradigm with mice, mice overexpressing the _____ _______ in the raphe showed ______ aggression.
intruder, 5-HT1A, autoreceptors, hyper
the ____ _____, _____, ____ and _____ mediate aggression and all express the 5-HT1A/B postsynaptic receptors and receive 5-HT inputs
cerebral cortex, hypothalamus, amygdala, striatum,
acute tryptophan depletion in healthy subjects can ____ aggressive behaviour in laboratory tests, resulting in more ____ by the subject against the opponent.
increase, attacks
increased aggression may be related to 5-HT regulation of
impulsivity
acting without adequate forethought, predisposition toward rapid, unplanned reactions without regard to their negative consequences
impulsivity
rat performs an attention task (a light flashes briefly in a certain location, rat must nosepoke it quickly to get reward)
5 choice serial reaction time task
5-HT is particularly important for mediating _____, and may act as a ____ to control impulsive responses.
waiting, brake
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 _____
5,7-DHT, premature responses, antagonists, agonists, drug addictions, ADHD
