lecture 10 LOs Flashcards
dopamine receptor subtypes amount and type
five subtypes, D1-5
all metabotropic
D1 and 5 are similar, D2-4 are similar
what does D1 dopamine receptor activation stimulate
adenylyl cyclase and cAMP synthesis
what does D2 domaine receptor activation do
reduces cAMP and inhibits adenylyl cyclase
what is the difference between where D1/D2 and D3/D4 receptors are found
D1/2 found in all brain regions that get DA innervation (but not necessarily both in all areas)
D3/4 receptors show more regional variations
what do D2 type receptors function as and what do their antagonists do
function as both autoreceptor and postsynaptic receptor
D2 antagonists increase DA release (by blocking the autoreceptor) but also reduce postsynaptic DA signalling
do D1 or D2 receptors have higher affinity for DA
D2
what does it mean that some DA receptors are _____ on glutamate/GABA terminals that _____
heteroreceptors
modulate fast transmission presynaptically
what does the DA agonist apomorphine do
stimulate D1 and D2 receptors
casues behavioural activation similar to that seen w cocaine or amphetamine
DA receptor agonists are used for treatment of parkinsons
what does DA antagonist flupenthixol do
blocks both D1-D2 receptors
reduces motivaton at higher doses produces catalepsy (lack of spontaneous movement) like all D1 or D2 antagonists
what does DA antagonist haloperidol do
highly selective for D2 vs D1 but will bind to the entire D2 like family similarily
what happens if D2 antagonist is given repeatedly over 12 days
rats develop behavioural supersensitivity
after chronic treatment the dose no longer is effective at blocking AMPH
then when the antagonist treatment is stopped the DA agonist has greater locomotor response
where are norepinephrine (NE) neuron cell bodies in the central nervous system
NE neuron cell bodies resude in the pons and medulla in the brain stem
locus coeruleus in the pons is a dene collection of NE neurons
where do NE anxons of the central nervous system extend to
nearly all of the forebrain as well as the cerebellum and the spinal cord
where is NE released from in the peripheral nervous system
sympathetic noradrenergic neurons at synapse like contacts
adrenal glands and travel in the bloodstream to target organs (cannot cross blood brain barrier)
NE receptor subtypes
alpha and beta
both metabotropic
distributed widely across cortical and subcortical sites
what do alpha1 receptors for NE operate w
phosphoinositide 2nd messenger system (post synaptic)
what are the a1 NE receptor agonist and antagonist
agonist: phenylephrine
antagonist: prazosin
what does the a2 NE receptor do
reduce cAMP synthesis (like a D2 receptor) and serves as presynaptic autoreceptor and postsynaptic receptor
what is the a2 NE agonist and antagonist
agonist: clonidine
antagonists: yohimbine
what do b1 and b2 NE receptors do
stimulare adenylyl cyclase and enhance synthesis of cAMP (like D2 receptors)
what are the agonist and antagonist of b2 NE receptor
agonist: isoprotenerol (increase heart rate)
antagonist: propanolol (decrease heart rate)
NE is key for maintaining arousal, waht happens to do this
Locus coerelus neurons fire more rapidly during waking vs sleep
almost completely silent in REM tho
what NE projections promote wakefulness
to medial septal and medial preoptic areas
what does a pharmacological increase in NE promote
anxiety like feelings
what does yohimbine do regarding NE release and beh effects
increases NE release, induces anxious like beh
what does NE regulate
congitive functions mediated by prefrontal cortex (attention and working mem)
what does activation of pre frontal cortex a2 receptors do
increases working memory impairments
likely happens via activation of postsynaptic a2 receptors, rather than via reduced NE release
NE facilitates ___ via activation of ___
PFC function
postsynaptic a2 receptors
stress causes what to happen to PFC NE levels
excessive increase
impaired cog function
steps of stress induced impairment in PFC function and a1-receptors
stimulate PFC a1 receptor impairs cognition
antagonizing PFC a1 receptor can increase stress induced impairments
NE has lower affinity for PFC a1 receptors vs a2 receptors
stress can induce larger than normal increases in NE levels which increases a1 receptor activation which leads to cog impairment
how do strong emotional states affect memory consolidation
enhance it
may be mediated NE in part
what does a beta adrenergic receptor antagonist do
disrupts enhancement of memory for emotional content (not neural content) but subjects still have an emotional response to the story
what do stressful events do to NE
increase its release in the amygdala
this can enhance consolidation of memories
can be part of PTSD
what can stress cause in the PFC
increase in NE levels which impair cognitive function
