What do the 5-HT6 and 5-HT4 receptors do? I haven't heard of them being useful for anhedonia before. Also, how would you target those specific receptors?
5-HT(6) receptors enhance GABA-ergic signaling as opposed to many other serotonin receptors that inhibit it, it's also the main serotonin receptor involved in alleviation of anxiety and OCD (!) - therefore activation of results in a "clean" anxiolytic effect....(!)
I don't believe any direct and specific agonists exist for 5-HT6 (other than R&D), but I'll keep looking.
5-HT(4) activation enhances dopamine in some area's of the brain (as well as histamine and acetylcholine (!)) but can also result in negative gastro-intestinal sides such as diarrhea/IBS etc...the only downside to activating this receptor is it could exacerbate anxiety issues so it is sort of opposite to the 5-HT6R's in some ways.
Prucalopride, which is a 5-HT(4) agonist; therefore stimulating prefrontal dopamine, plus hippocampal/prefrontal histamine and acetylcholine - can be bought at TeamTLR's shop here.
Antagonists, which would help diarrhea and anxiety on the other hand, would be L-Lysine (!) and Chamomile(!).
Therapeutic Applications of 5-HT4Receptor Agonists and Antagonists(http://link.springer...-662-05553-3_10)
Metoclopramide is used to stimulate ‘upper gut’ motility and prevent nausea and vomiting. These clinical benefits are attributed, respectively, to 5-HT4 receptor activation23 and to antagonism at dopamine D2 and/or 5-HT3 receptors.52 However, since antagonism at dopamine D2 receptors within the striatum may also cause extrapyramidal reactions and akathisia, alternative 5-HT4 receptor agonists have been developed, with lower affinity for the D2 receptor. The most notable is cisapride. Metoclopramide and cisapride are marketed for gastrointestinal hypomotility disorders such as gastro-esophageal reflux (heartburn; mild esophagitis), functional or nonulcer dyspepsia and gastroparesis (e.g., caused by diabetic neuropathy).7 For both drugs, the most common side-effect attributed to 5-HT4 receptor activation is the promotion of loose stools and in more severe cases, diarrhea and abdominal pain.
That's the first time I've heard of the amygdala and hypothalamus being implicated in anhedonia. Can you post the studies please?
I suggest you read this book, it's free, just go to link, already there.
::.... Neurobiological mechanisms of anhedonia :...:.::
The orbitofrontal cortex is a nexus for sensory integration, the modulation of autonomic reactions, and anticipation in learning, prediction and decision-making for emotional and reward-related behaviours.[/size]50[/size]Ncuroimaging studies have found that the reward value,[/size]51[/size] and the expected reward value,[/size]52[/size] and even the subjective pleasantness of food[/size]53[/size] and other reinforcers are represented in the orbitofrontal cortex. The orbitofrontal cortex receives input from the five classic sensor}' modalities: gustatory, olfactory, somatosensory, auditory, and visual,[/size]54[/size] and also receives visceral sensory information. This large variety of inputs makes the orbitofrontal cortex one of the most polymodal regions in the entire cortical mantle.[/size]53[/size] The orbitofrontal cortex has direct reciprocal connections with other brain structures, including the amygdala, cingulate cortex, insula/operculum, hypothalamus, hippocampus, striatum, periaqueductal grey, and dorsolateral prefrontal cortex. Hence, the orbitofrontal cortex may have an important role for representing incentive salience, hedonic impact, and subjective hedonic experience, ic, constituting the link between reward and hedonic experience.[/size]53[/size]
It has been shown that the human amygdala is a key structure for extracting the affective significance from external stimuli,55 responds preferentially to emotionally valenced faces, for fearful but also for happy faces, and rapidly habituates to them.56 According to discrepant findings,57,58 the amygdala could be considered as reacting more intensively for negative stimuli, explaining its major function in fear and anxiety.
Also, how can you lower cortisol / ACTH levels and regenerate the dopaminergic system?
Lowering cortisol and ACTH would be by using adaptogenic herbs such as rhodiola rosea, ashwagandha, and gotu kola...alternatively, you can use a 'strong' direct cortisol blocker such as PES Erase or SNS Reduce XT.
You also need to raise your stress threshold and decrease overall exposure to stressful situations....leaning out and hitting the gym regularly will help as well.
As far as dopamine, yes, 9-me-BC what I was referring to. You can also do a specific carboline intake method, take 9-me-bc 7 days on, then take 2 days off and use maca powder which contains beta-carboline alkaloids - the point is using complex substances that regenerate the hypothalamus and then to move back to central functioning I.E the dopamine networks .
Edited by Area-1255, 16 April 2015 - 02:37 AM.
LongeCity
