lecture 18 LOs Flashcards
what is the NT adenosine a key modulator of
drowsiness
what type of NT is adenosine
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
where does extracellular adenosine come from
ATP released from inside cells and is then broken down to adenosine, which stimulates extracellular receptors
at typical doses what does caffeine act as
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
where are the adenosine alpha2A receptors found, and what do they form
found on GABA output neurons in the dorsal/vental striatum
form heteromers with the D2 receptors
what can activation of the alpha2A receptors do
reduce affinity of D2 receptors for DA, decreasing arousing/behaviourally activating effects of DA
what can caffeine do by blocking adenosine receptors
- enhance D2 signalling, leading to mild arousal and psychomotor activation
- reduce inhibitory effect of adenosine on other post-synaptic neurons and presynaptic glutamate terminals, increasing neural activity
what is major unipolar depression characterized by
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
what can trigger unipolar depression episodes
external events (reactive), or occur with no apparent cause (endogenous)
when is depression considered pathological
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)
what are the costs to individuals and societies with depression
dramatically increased risk of suicide
impact on relatives/friends of the individual with depression
lost productivity costs
how does unipolar depression ebb and flow
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
what is the prevalence of unipolar depression
15-20% of the population may be afflicted at any one time
sex differences of depression
women are more likely to be diagnosed and incidence often coincides with major hormonal changes (postpartum or menopause)
how do stress and anxiety play into depression
depression is viewed as a stress-related disorder and is closely related with anxiety
intense stress and anxiety often precede depression
how do alterations in the HPA axis and in CRF levels affect depression
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
if you have cushings syndrome, what are you at a higher risk for and why
depression because of high levels of glucocorticoids
what is the test that can show excessive CORT release
the dexamethasone suppression test
dexamethasone is a synthetic glucocorticoid that can suppress CORT release in normal people but not in depressed patients
where in the brain is there increased blood flow in depressed people
in the amygdala and the ventral medial prefrontal cortex
amygdala: increased anxiety
where has reduced volume been seen in the brain to correlate with depression
in the hippocampus
what is the glucocorticoid hypothesis for depression
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
what do glucocorticoids do
increase hippocampal excitability
high, sustained levels can cause atrophy oh hippocampal/PFC neurons
what does impaired hippocampal function lead to
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
what does chronic mild stress do to animal models
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)
