Lecture 16 - Dopamine Flashcards
What are the Dopamine receptors (GPCRs)?
-families of receptors D1 and D2
-D1 and D5 (Gi/Go)
-D2; D3; D4 (Gq)
What has been found about placebo effect for Parkinson’s?
-study in Vancouver looking at L-DOPA
-found that a large number of patients that got sugar pill had reduced tremors and more dopamine (MRI)
Which of the dopamine receptors can be an autoreceptor?
-only D2 can be an autoreceptor
-located on the presynaptic neuron
-mainly found in dorsal and ventral striatum [very few D2 autoreceptors in PFC]
How does the D2 autoreceptor work?
-play a crucial role in regulating the release of NT like DA.
-act as a negative feedback mechanism [thermostat] to maintain optimal DA levels within the synaptic cleft
What happens when DA levels in the synapse rise?
-DA molecules bind to D2 autoreceptors on the presynaptic neuron
-which then phosphorylates TH
-phosphorylation of TH reduces its activity, slowing down the production of new DA
-reduces the amount of DA available for release into the synapse
Where does DA bind?
-D2 autoreceptors have a higher affinity for DA than postsynaptic D2 receptors
-meaning that dopamine is more likely to bind to autoreceptors first
What is an example of autoreceptor doses of agonists?
-apomorphine, a D2 agonist
-in very low doses, apomorphine preferentially binds to the high-affinity D2 autoreceptors, triggering the negative feedback loop and suppressing DA synthesis and release
-leads to decreased DA transmission, and apomorphine acts as an indirect antagonist at these low doses
What happens when apomorphine is at moderate doses?
-at moderate doses, apomorphine saturates the autoreceptors and also binds to the postsynaptic D2 receptors,
-resulting in increased DA transmission
What do DA transporters do?
-DA transporter plays a role in clearing dopamine from the synapse
-drugs like cocaine and amphetamines interfere with the dopamine transporter
What do cocaine and amphetamines do to DA transporters?
-cocaine blocks the transporter, preventing DA reuptake and prolonging the DA signal [ritalin also blocks]
-amphetamines reverse the transporter, causing DA to be pumped out of the neuron into the synapse
What are the effects of cocaine and amphetamines on signal transmission?
-effects of cocaine are signal-dependent, meaning they enhance the effects of existing DA release
-effects of amphetamines are signal-independent, meaning they can cause DA release even in the absence of neuronal firing
Who is Roy Wise?
-he came up with the dopamine hypothesis of reward
-stating that dopamine [in the mesocorticolimbic pathway] is involved in reward, but it is actually involved in motivation and saliency
What are the roles of the Mesocorticolimbic system?
-inhibition
-decision-making
-executive functions (STM; planning; working memory; etc.)
What affects working memory?
-DA levels in the PFC are critical for optimal working memory
-both too much and too little DA can impair working memory
-relationship between DA levels and working memory resembles the Yerkes-Dodson law, which states that there is an optimal level of stress for peak performance
What is believed to play a role in ADHD?
-ADHD is thought to involve a delay in PFC development, resulting in insufficient DA levels in this area
