lecture 18 LOs Flashcards

1
Q

what is the NT adenosine a key modulator of

A

drowsiness

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2
Q

what type of NT is adenosine

A

primarily an inhibitory NT, can act on both postsynaptic neurons and on presynaptic glutamate terminals
adenosine levels in the brain tend to be lowest after waking from sleep, increase over the day that may serve as a type of sleep time clock

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3
Q

where does extracellular adenosine come from

A

ATP released from inside cells and is then broken down to adenosine, which stimulates extracellular receptors

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4
Q

at typical doses what does caffeine act as

A

an adenosine receptor antagonist
caffeine has other neural effects but at higher doses than typically ingested
four adenosine receptors have been identified and stimulant effects of caffeine are primarily on the alpha2A subtype

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5
Q

where are the adenosine alpha2A receptors found, and what do they form

A

found on GABA output neurons in the dorsal/vental striatum
form heteromers with the D2 receptors

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6
Q

what can activation of the alpha2A receptors do

A

reduce affinity of D2 receptors for DA, decreasing arousing/behaviourally activating effects of DA

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7
Q

what can caffeine do by blocking adenosine receptors

A
  1. enhance D2 signalling, leading to mild arousal and psychomotor activation
  2. reduce inhibitory effect of adenosine on other post-synaptic neurons and presynaptic glutamate terminals, increasing neural activity
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8
Q

what is major unipolar depression characterized by

A

unhappy mood (more an absence of happiness than increased sadness), worthlessness, guilt, desperation
loss of interest, energy/motivation, appetite, pleasure (anhedonia)
difficulty in concentration, restless agitation

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9
Q

what can trigger unipolar depression episodes

A

external events (reactive), or occur with no apparent cause (endogenous)

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10
Q

when is depression considered pathological

A

when symptoms are disproportionate/prolonged
high comorbidity of depression with other medical conditions.metnal disorders (anxiety, alcohol dependence)
symptom clusters vary with individuals (there may be depression subtypes associated with distinct causes and pathophysiologies)

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11
Q

what are the costs to individuals and societies with depression

A

dramatically increased risk of suicide
impact on relatives/friends of the individual with depression
lost productivity costs

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12
Q

how does unipolar depression ebb and flow

A

alternates with normal states, episodes can last up to 6-9 months
episodes can recur through life, often increasing in frequency and intensity
sometimes depressive episodes can end on their own

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13
Q

what is the prevalence of unipolar depression

A

15-20% of the population may be afflicted at any one time

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14
Q

sex differences of depression

A

women are more likely to be diagnosed and incidence often coincides with major hormonal changes (postpartum or menopause)

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15
Q

how do stress and anxiety play into depression

A

depression is viewed as a stress-related disorder and is closely related with anxiety
intense stress and anxiety often precede depression

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16
Q

how do alterations in the HPA axis and in CRF levels affect depression

A

some forms of depression may be linked to alterations in the HPA axis and higher CORT levels as well as CRF levels
CRF is a stress-related peptide transmitter in brain that affects numerous limbic brain regions and stimulates cortisol release

17
Q

if you have cushings syndrome, what are you at a higher risk for and why

A

depression because of high levels of glucocorticoids

18
Q

what is the test that can show excessive CORT release

A

the dexamethasone suppression test
dexamethasone is a synthetic glucocorticoid that can suppress CORT release in normal people but not in depressed patients

19
Q

where in the brain is there increased blood flow in depressed people

A

in the amygdala and the ventral medial prefrontal cortex
amygdala: increased anxiety

20
Q

where has reduced volume been seen in the brain to correlate with depression

A

in the hippocampus

21
Q

what is the glucocorticoid hypothesis for depression

A

focuses on the stress-related neuro-endocrine abnormalities of depression
hypothalamic CRF neurons are regulated by other nuclei (the amygdala stimulates and the hippocampus inhibits)
early life stress can increase CRF expression in the hypothalamus, increases amygdala sensitivity to stress and decrease glucocorticoid receptors in the hippocampus

22
Q

what do glucocorticoids do

A

increase hippocampal excitability
high, sustained levels can cause atrophy oh hippocampal/PFC neurons

23
Q

what does impaired hippocampal function lead to

A

loss of inhibitory regulation of HPA axis
may also contribute to behavioural syndrome in depression where patients often report being unable to remember a time where they were happy
antidepressant drugs reduce CRF levels and reverse loss of hippocampal dendrites in animal studies

24
Q

what does chronic mild stress do to animal models

A

rodent exposed to multiple different types of stressors (cold temps, wet bedding, restraint, sudden loud noises) over 1-3 weeks (so that the animal cannot habituate to one form of stress)

25
Q

what does chronic social defeat do to animal models

A

have an intruder rat/mouse fight a more dominant conspecific-repeated experiences with defeat can induce depression

26
Q

what does early maternal separation do to animal models

A

young animals are separated from their mothers for brief periods daily during the first few weeks of life

27
Q

what does the forced swim test show in animal models

A

models behavioural despair, immobility is thought to reflect a passive coping strategy
acute antidepressant treatment reduces immobility and increases active coping strategy (swimming, climbing) in normal animals

28
Q

what does social avoidance do in animal models

A

typically used with social defeat model
rodents avoid conspecifics after repeated defeats

29
Q

what does sucrose preference do to animal models

A

models anhedonia
depression models reduce preference for sucrose solution vs water
chronic antidepressants can reverse this effect

30
Q

what can early life stressors do to brain regions to cause depression

A

can make HPA axis over responsive and increase the risk for depression

31
Q

what is seen in adult rats who are subjected to early life trauma

A

higher stress induced cortisol and CRF release as adults
greater depressed like behavious

32
Q

what does antidepressant treatment prevent in animals

A

prevents cortisol/CRF increase in adults
reduced depressed like behaviour
when treatment was terminated all the abnormalities returned

33
Q

what are some key drugs in the monoamine hypothesis of depression

A

reserpine: drug that reduce monoamine levels induces depression
monoamine oxidase inhibitor: blocks metabolism of monoamines and increase brain levels alleviated depression
impramine: first tricyclic antidepressant, blocks monoamine reuptake, effective in alleviating depression
fluoxetine (SSRI, Prozac): found to be effective at treating depression
***depression is the result of abnormal reductions in brain monoamine (mostly serotonin and noradrenaline) levels

34
Q

what are four limitations of the monoamine hypothesis

A
  • antidepressants increase monoamine levels quickly yet there is a long lag between drug treatment and reduction of symptoms
  • not all depressed patients respond to drugs that increase monoamine levels
  • depletion of serotonin or NE does not cause a depressive-phenotype in animal models
  • tryptophan depletion induce symptoms of depression in unmedicated depressed patients (in remission) or health subjects with family history of depression but NOT IN SUBJECTS WITHOUT FAMILY HISTORY OF DEPRESSION