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Re: How do SSRIs normalise the amygdala?

Posted by linkadge on February 16, 2018, at 18:33:29

In reply to Re: How do SSRIs normalise the amygdala?, posted by Christ_empowered on February 16, 2018, at 10:19:41

When given in the short term, SSRIs do appear to increase serotonin in the synapse. However, this activates autoreceptors which in turn reduces the subsequent release of serotonin. Also, many antidepressants have anti-inflammatory effects. Reducing inflammation also tends to reduce serotonin release. Also, chronic activation of 5-ht1b autoreceptors can reduce serotonin synthesis.

Here is a study in which mice lacking Tph2 (i.e. mice who are already low in serotonin) given SSRIs experienced a further lowering of serotonin levels.

"Thus, it is reasonable to expect that the ability of chronic reuptake inhibitors to induce monoamine depletions could be exacerbated under conditions of deficient monoamine synthesis machinery."

Here is another study in which citalopram administration resulted in reduced serotonin synthesis.

"Chronic Citalopram Administration Causes a Sustained Suppression of Serotonin Synthesis in the Mouse Forebrain"

They hypothesize "Although SSRI treatment produces robust increases in extracellular 5-HT, there is evidence that SSRI administration can actually deplete brain stores of 5-HT and of its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) [64], [69][77], as would be predicted if 5-HT synthesis were suppressed and serotonergic neurons were unable to effectively recapture released 5-HT."

Another interesting excerpt, from the book "Neurobiology of Depression", which references over 50 additional studies...

"In contrast to this prevailing hypothesis of antidepressant mechanism of action, we found that half of the approximately 50 studies that have been carried out using in vivo microdialysis fail to report increases in extracellular serotonin levels in response to chronic antidepressant administration in mice and rats"

As far as the amygdala, I'm not sure. It could be that with chronic administration the SSRI is actually reducing serotonin (or at least normalizing serotonin). It could also be that other targets of the drugs have an impact on the amygdala. For example, many SSRIs increase the level of a neurosteroid called allopregnanalone. This substance increases gaba signaling, and could be reducing amygdala activity.

Serotonin is actually a stress hormone of sorts. Anxiety is often seen as a high serotonin state. Many anti-anxiety medications actually lower serotonin release (i.e. benzodiazapines, buspar) or block specific serotonin receptors (5-ht2a/c, 5-ht3). Even activating 5-ht1a receptors increases cortisol (i.e. the cortisol response) although the receptors can become desensitized to this effect.
It's probably a cop out answer to say that its the right amount of serotonin, at the right receptors, for the right length of time which causes the ideal level of stress needed to respond and adapt behaviorally to stressful situations.
But, it's way, way, way more complicated than I can grasp.





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