Pysch Exam 4: ADHD (Sartor)

how does PFC regulate "top-down attention"?

-sustain attention especially during boring conditions

-focus on important material and ignoring irrelevant small stimuli/noise

-shift attention when multi-tasking

PFC in ADHD

decreased volume in these pts

striatum dysfunction in ADHD

deficits in motivation, predicting outcomes, completing tasks

cerebellum dysfunction in ADHD

smaller volume for attention shifting, working memory, timing

catecholamine receptors in PFC in untreated ADHD

too little NE alpha 2 or D1 activity

drowsy effects

catecholamine receptors in PFC in excessive doses of ADHD stimulants

excess NE alpha 2 and D1 activity

stressed

DA and ADHD

decreased levels in striatum and PFC

NE and ADHD

PFC

DA functions

-motivation

-memory

-attention (focus, acquisition on info, on-task behavior)

NE functions

-proper attention shifting

-executive functions

how to HCN channels work

they act like leak channels- reduce signals when open (are leaking signal) or increase the signal when closed

MOA of HCN channels

- activated/ opened by cAMP

-open HCN has cations leak out so info doesn't make it to the cell body

-DA/ D1R and NE/alpha 2 R regulate HCN activity

most ADHD drugs do what

stimulate D1 and/or alpha 2 receptors

DA and NE in the PFC

they both regulate glutamate signals at the post-synaptic dendritic spines in the PFC

NE effect on signal

strengthens signal

MOA of NE on signal

1. NE binds to alpha 2

2. this inhibits cAMP

3. HCN closes and the signal is strengthened

MOA of DA on signal

1. DA binds to D1

2. cAMP increased which opens HCN channels

3. signals weakened but this reduces the noise at glu neurons in the PFC

effect of DA on signal

weaker signal that reduces the noise

yohimbine MOA

blocks alpha 2 receptors which showed similar profiles in monkeys to ADHD patients

MOA of Adderall (3 dextro: 1 levo)

inhibit DAT, NET, and SERT

methylphenidate brand name

ritalin

MOA of methylphenidate

inhibit DAT and NET

lower misuse potential due to small effects on DA in ventral striatum

atomoxetine brand name

strattera

MOA of atomoxetine

NET inhibitor

less effective/non-stimulant bc doesn't directly increase DA

modafinil brand name

provigil

MOA of modafinil

-weak DA and NE reuptake inhibitor

-activates orexin and histamine neurons indirectly

modafinil in ADHD

-sometimes used off-label

-degree of improvement is likely related baseline intelligence because it didn't help vigilance/memory in the most intelligent cohort

other drugs used in kids and their MOAs for ADHD

viloxazine (SNRI)

guanfacine (NE alpha 2 agonist)

bupropion (NET/DAT inhibitor)

amantadine (increase DA etc)