lecture 19 LOs Flashcards
what other things does serotonin play a role in
pain sensitivity, emotionality, response to negative/positive events
what does the short allele in SERT genes associate with
reduced transporter function (higher levels of serotonin)
observed in some types of depression- may be linked to some forms of depression brought on by stress
higher levels of serotonin can reduce firing of serotonin neurons via autoreceptor mediated inhibition
what do mutant mice with reduced SERT functioning show
lower basal activity of raphe serotonin neurons
what do depressed patients show regarding serotonin agonists
reduced sensitivity to serotonin agonists
this can be reversed with chronic antidepressants treatment
what does acute SSRI treatment do to serotonin
increases it by blocking reuptake
this activates somatodendritic autoreceptors to slow cell firing and reduce serotonin release
what does long-term SSRI treatment do to serotonin release
down regulates autoreceptors so the drugs can in turn increase synaptic serotonin release
what does repeated SSRI treatment do to serotonin
increase sensitivity of certain postsynaptic serotonin receptors in the PFC and the hippocampus
what does NE play a key role in regarding depression
neuroendocrine function, reward mechanisms, attention/arousal, stress response
what does chronic antidepressant treatment do to NE levels
down regulates postsynaptic beta receptors and alpha2 autoreceptors
this lag parallels the onset of therapeutic response
downregulation of alpha2 receptors not always seen in treated patients
what did the first class of drug used to treat depression do
inhibit MAO allowing more NT to be available for release
use is now limited because of sleep disturbances, weight gain, increased blood pressure, interactions with other meds
what do tricyclic antidepressants do
block presynaptic transporters to inhibit reuptake of monoamines, which prolongs the duration of transmitter action at the synapse
what are the side effects of tricyclic antidepressants
many TCAs block histamine receptors causing sedation and fatigue
anticholinergic effects like drymouth, constipation, urine retention, dizziness, confusion
some TCAs block alpha1 adrenergic receptors, and when combined with NE reuptake blocking can leading to dangerous cardiovascular effects
TCAs have low therapeutic index: fatalities occur at approx ten times the normal dose
what causes SSRIs to be more efffective
mediated by increased activation of some serotonin receptors
activation of other receptors can lead to anxiety, movement disorders, nausea, headache, insomnia, sexual dysfunction
what is serotonin syndrome
dangerous effects when SSRIs combined with other serotonin agonists or drugs that interfere with SSRI metabolism
agitation, disorientation, ataxia, spasms, fever
can SSRIs cause physical dependence and withdrawal
yes
