Re-assessing the catecholamine hypothesis of depression: the case of melancholic depression Flashcards
What hypothesis is proposed regarding major depression and norepinephrine (NE)?
Major depression represents a deficiency of norepinephrine (NE) at critical synapses in the central nervous system.
How does imipramine affect norepinephrine neurotransmission acutely?
Imipramine acutely increases NE neurotransmission.
What is one chronic effect of imipramine on norepinephrine turnover?
Increased NE turnover in the brain.
What effect does long-term treatment with imipramine have on stress response?
Reduces the stress-induced increase in extracellular norepinephrine concentrations in the prefrontal cortex of rats.
What is the anxiolytic effect of chronic imipramine administration?
Antagonizes the increase in norepinephrine output caused by anxiogenic stimuli.
Fill in the blank: MAO inhibitors block the metabolism of NE, hence increasing _______ neurotransmission.
NE
What is the effect of reserpine on norepinephrine?
Reserpine depletes NE from noradrenergic neurons.
In melancholia, how is noradrenergic neurotransmission and locus caeruleus activity characterized?
Increased rather than decreased.
What defines melancholia in contrast to typical depression?
A state of hyperarousal and a tortured sense of worthlessness.
What are some effects of norepinephrine relevant to melancholic depression?
- Promotes anxiety and hyperarousal
- Stimulates corticotropin-releasing hormone (CRH)-mediated hypercortisolism
- Is neurotoxic
- Promotes insulin resistance
- Mediates bone loss
What levels are increased in patients with melancholic depression?
Increased CSF and plasma levels of NE.
What is the relationship between CRH and the locus caeruleus/NE systems?
CRH stimulates the locus caeruleus, while NE stimulates CRH release.
What role does yohimbine play in norepinephrine secretion?
Yohimbine is an alpha-2 noradrenergic antagonist that increases the secretion of plasma NE.
How do multiple tricyclic antidepressants affect locus caeruleus neurons?
Decrease the basal and sensory-evoked firing rates.
What is the effect of antidepressants like fluoxetine on serotonergic neurotransmission?
They decrease the locus caeruleus firing rate.
Fill in the blank: Activation of serotonergic receptors inhibits _______ activity.
locus caeruleus
What happens to beta-noradrenergic receptors in the brain with multiple antidepressants?
They are down-regulated.
What was the initial hypothesis about norepinephrine in major melancholic depression?
That NE was deficient.
What conclusion was drawn about locus caeruleus activity in melancholic depression?
That it is actually increased rather than decreased.
How does norepinephrine affect corticotropin-releasing hormone (CRH)?
NE stimulates CRH release.
What is observed in patients with atypical depression regarding hypothalamic CRH activity?
Evidence of reduced hypothalamic CRH activity.
What is a possible implication for patients with atypical depression regarding noradrenergic function?
They may have decreased noradrenergic function.
