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Comment · Sat, April 27, 2013 · Ceretropic

Nootropics that Increase Emotional Response?

Original post in this thread

[deleted] · 21 points

runnerboy's thread piqued my curiosity. Emotion is a large part of being human, and as tempting as it is to be rational as can be, emotion brings many advantages. Being more in touch with one's emotions has the potential to improve sympathy for others, and even empathy in difficult situations. This, in turn, can improve one's social life, and -- being social creatures -- is beneficial for neurological health (in terms of general well-being and mood, which can make all the difference in terms of motivation and productivity). What's the point of being extremely logical/rational if you're friendless? Emotions have the capacity to improve our lives.

Are there any nootropics (or maybe compounds not thought of as nootropics) that improve emotional ability, response, or awareness?

My first guess is perhaps Naltrexone (low-dose). Be it physical or emotional pain, the brain's response is the same. Increased basal endorphin levels could improve capacity for relating to others... maybe? I don't know much about this. (That's why I'm wondering what you guys think!)

What they were answering

AtomikPi · 5 points

I'm a bit confused. You're saying down regulation can lead to depression. But do SSRIs up- or down-regulate? Now I'm aware that increasing extracellular 5-HT should downregulate 5-HT2a, but I also remember reading that some types of serotonin receptors are upregulated by SSRIs.

So do we conclude that SSRIs upregulate and therefore help treat depression? But in that case, wouldn't we expect SSRIs to induce schizophrenia in some cases? And in that case, how do you explain the ability of adrenergic drugs in treating depression with equal efficacy? IE bupropion is primarily a NE releasing agent, and it manages to alleviate depression with equal efficacy to the SSRIs. Presumably, this is via some downstream effect - alleviation of the stress response, hippocampal neurogenesis - something like that.

u/MisterYouAreSoDumb · Ceretropic

We are simplifying a very complicated disorder. Some SSRIs down-regulate receptors, while others up-regulate. SSRI's main antidepressant action is not one of up-regulation, though.

Traditional thought is that the increase in extracellular 5-HT is the cause of SSRI mediated results. However, recent research has concluded that it is due to another regulatory mechanism; possibly BDNF related.

http://www.fasebj.org/content/22/6/1702.long

This delay suggests that it is not simple serotonin uptake inhibition per se, but rather additional regulatory mechanisms that may underlie the therapeutic effect. These mechanisms are thought to include 5-HT-mediated elevated expression of neurotrophic factors such as brain-derived neurotrophic factor (BDNF), which, in turn, enhance the sprouting of serotonergic axons (8⇓ , 11⇓ 12⇓ 13)⇓ . Another mechanism is thought to rely on the regulation of the efficiency of the clearance of 5-HT from the extrasynaptic space by modulation of SERT protein expression on the cell surface. In this regard, it has been reported that long-term treatment with SSRIs leads to a significant reduction of SERT density in hippocampal and dorsal raphé slices in rats (14⇓ , 15)⇓ .
And in that case, how do you explain the ability of adrenergic drugs in treating depression with equal efficacy?

Because not all depression arises from the same mechanism. Also, treating symptoms can provide clinically equivocal benefits, without actually combating the cause.

Depression is a very complicated moving target. Having gone through it, I can say that doctors have their work cut out for them. When you are in a deep depression, it's very hard for others, including trained professionals, to accurately assess the situation and provide a treatment plan. It's not nearly as simple as, "your 5-HT receptors are down-regulated" or "your body cannot produce enough 5-HT." Many of the different systems are intertwined, which is why different mechanisms provide different efficacies to different people.

wouldn't we expect SSRIs to induce schizophrenia in some cases?

No, what I meant to say was that up-regulation of 5-HT2A receptors can cause schizophrenic symptoms, not actual schizophrenia.

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