aced126
Bluelighter
- Joined
- May 18, 2015
- Messages
- 1,047
I've always wondered why serotonin reuptake inhibitors produce a distinctly different behavioural response to serotonin releasing agents. Even at high doses, no sort of empathic or rewarding response is elicited by SSRIs, unlike SRAs. Furthermore, why is it that DA reuptake inhibitors like methylphenidate produce similar responses to DA releasers like amphetamine (actually a lot of compounds thought to be reuptake inhibitors like cocaine are now believed to act on DAT in a different way, causing a sort of inverse agonism and not exactly just reuptake inhibition per se. But I'll just leave the point about DA in anyway). Is it something to do with the kinetics of 5HT release? Releasers essentially force the presynaptic neuron to propogate the action potential at all times, but the post-synaptic neuron can only fire as fast as its maximum frequency. Reuptake inhibitors can't initiate an action potential and the presynaptic neuron needs to actually fire on its own to get the NTs in the synaptic cleft anyway. Could it be that some 5HT neurons fire quite infrequently and a SERT blocker won't do much because there isn't much 5HT in the cleft anyway.
Secondly, if one were to administer serotonin directly into the brain (too much ADME issues with oral), would it elicit a response similar to a serotonin releaser? I have a feeling it wouldn't. Although releasers release serotonin, is it correct to assume that the density of SERT is uniform across all serotonergic terminals (I'm guessing not). If this is the case, then at terminals where SERT is densely expressed, direct serotonin will just be taken up faster, whereas releasers will actually increase serotonin transmission into the synaptic cleft, because they make SERT transport in reverse.
Of a different topic, some peptide hormones synthesised in the brain like ACTH and vasopressin, and are secreted into the blood. How are they able to cross the BBB? Are there specific transporters for each protein?
Secondly, if one were to administer serotonin directly into the brain (too much ADME issues with oral), would it elicit a response similar to a serotonin releaser? I have a feeling it wouldn't. Although releasers release serotonin, is it correct to assume that the density of SERT is uniform across all serotonergic terminals (I'm guessing not). If this is the case, then at terminals where SERT is densely expressed, direct serotonin will just be taken up faster, whereas releasers will actually increase serotonin transmission into the synaptic cleft, because they make SERT transport in reverse.
Of a different topic, some peptide hormones synthesised in the brain like ACTH and vasopressin, and are secreted into the blood. How are they able to cross the BBB? Are there specific transporters for each protein?
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