Question

You are developing a new drug to treat Major Depressive Disorder (MDD). You know that patients do not show clinical signs of improvement when they begin taking an SSRI. Your goal is to create a drug that will result in immediate improvement for patients, and can be used with SSRIs initially, and discontinued once the SSRI becomes fully effective. (10 points total)

a. Explain how SSRIs affect transmission at serotonin synapses, and why clinical effects are not seen immediately after a patient starts taking this medication. (6 pts)

b. What part of neuronal transmission would you target with your drug? Why would this alleviate the issue with SSRIs? (NOTE: Your answer should be logical and specific, and draw on what we have covered about communication between neurons this module/semester.) (4 pts)

In the first unit of this module, we discussed the neural basis for learning and memory. (10 points total)

a. What connection does the magnesium block on NMDA channels have to the principle of ‘threshold dependency’ for forming new memories? (3 pts)

b. List one similarity and one difference between the role of NMDA and AMPA channels in the process of LTP. (2 pts)

c. What role does calcium play in LTP? (1 pt)

d. Whereas LTP is an increase in the effectiveness of synapses, LTD is a process by which specific sets of synapses are selectively weakened. Calcium is involved in both LTP and LTD. Explain how different concentrations of calcium would lead to LTP vs. LTD. Be specific in your response, including the enzymes activated by calcium and the downstream changes to the number of receptors embedded in the postsynaptic membrane. (4 pts)

Answer 1

a). SSRIs treat depression by increasing levels of serotonin in the brain. ... SSRIs block the reabsorption (reuptake) of serotonin into neurons. This makes more serotonin available to improve transmission of messages between neurons. SSRIs are called selective because they mainly affect serotonin, not other neurotransmitters...

The reason suggested is that SSRIs don't target the serotonin transporter directly. Although some SSRIs (for instance, Lexapro) bind directly to the transporter, the direct binding is not the underlying mechanism of action. Instead antidepressants target our DNA, in particular the genes that code for the serotonin transporter. They make these genes less active, so fewer serotonin transporter molecules are available in the brain. This, it is argued, explains the delayed action of antidepressants.

Since our brain has plenty of active serotonin transporter molecules when we start taking antidepressants, it takes a while before a suppression of the genes that code for the transporter has an effect on serotonin in the brain. When we start taking the medication, our brain is like a refrigerator stocked with our old food choices. It takes a few weeks for us to get through that food and replace it with the healthier alternatives that can ultimately stabilize us and make us function optimally......