Matt the Raver
Bluelighter
- Joined
- Oct 7, 2006
- Messages
- 50
My main motive for posting this thread is to clarify the role that serotonin plays in the nervous system.
Firstly here's a scary reference. This is a VERY big review article on serotonin receptors.
Neuropharmacology 38 1083-1152 (1999) Barnes & Sharp. A review of central 5-HT receptors and their function
It's about 7 years old, so it might be a bit dated in places, but it's a very good overview for anyone who wants to understand how serotonin works.
Firstly, it's important to point out that cells that make serotonin (and other monoamines such as dopamine or noradrenaline) are only a tiny proportion of the total number of brain cells.
The vast majority of neurones in the brain are either glutamatergic or GABAergic.
One consequence of this is that serotonin tends to be released far more widely than GABA or glutamate a bit like a sort of 'neural aerosol'.
http://en.wikipedia.org/wiki/Serotonin
It also means that whereas Glutamate and GABA are important for transmitting specific information, monoamines are more important for 'fine tuning' neural activity, either increasing or decreasing it.
There are to my knowledge 14 different serotonin receptors, all with different properties, expressed in different parts of the brain. This means that any drug which increases serotonin release will cause very complex changes in activity.
This also means being able to classify receptors into different groups and define their distribution as very important to understand what serotonin's actually doing.
The first group are called 5HT1 receptor. There are 5 of them, termed A,B,D,E and F.
They're G protein coupled receptors and bind to Gi. Inhibiting proteins which increase cellular activity (Such as CAM Kinase II) and stimulating K+ channels, which also reduces cellular activity.
5HT1 receptors have the highest affinity for serotonin and so are therefore presumably the most active receptor type under normal conditions.
5HT1A seems to be important in affecting mood, as 5HT1A antagonists cause anxiety. Agonists (such as buspirone) have mild anxiolytic effects.
This in part seems to be due to inhibition of GABAergic neurones in the hippocampus (this inhibits inhibitory inputs, a process called DISINHIBITION) and causes an overall increase in hippocampal activity.
Also blocking amygdaloid activity which reduces anxiety.
Synapse. 2000 Dec 1;38(3):328-37
J. Neurosci. 1997 Jul 17(14) 5591-5598
5HT1 receptors also act as autoreceptors, inhibiting further serotonin release. It has been proposed that this is one of the reasons why SSRI antidepressants take about 2 weeks to have any theraputic effect is due to the time taken for the desensitisation of autorecepetors.
Riad et.al. J Neurosci. 2004 Jun 9;24(23):5420-6.
Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18F]MPPF in the nucleus raphe dorsalis of rat
I think this is going to get VERY long for a single post. So I'll continue in another one!
Firstly here's a scary reference. This is a VERY big review article on serotonin receptors.
Neuropharmacology 38 1083-1152 (1999) Barnes & Sharp. A review of central 5-HT receptors and their function
It's about 7 years old, so it might be a bit dated in places, but it's a very good overview for anyone who wants to understand how serotonin works.
Firstly, it's important to point out that cells that make serotonin (and other monoamines such as dopamine or noradrenaline) are only a tiny proportion of the total number of brain cells.
The vast majority of neurones in the brain are either glutamatergic or GABAergic.
One consequence of this is that serotonin tends to be released far more widely than GABA or glutamate a bit like a sort of 'neural aerosol'.
http://en.wikipedia.org/wiki/Serotonin
It also means that whereas Glutamate and GABA are important for transmitting specific information, monoamines are more important for 'fine tuning' neural activity, either increasing or decreasing it.
There are to my knowledge 14 different serotonin receptors, all with different properties, expressed in different parts of the brain. This means that any drug which increases serotonin release will cause very complex changes in activity.
This also means being able to classify receptors into different groups and define their distribution as very important to understand what serotonin's actually doing.
The first group are called 5HT1 receptor. There are 5 of them, termed A,B,D,E and F.
They're G protein coupled receptors and bind to Gi. Inhibiting proteins which increase cellular activity (Such as CAM Kinase II) and stimulating K+ channels, which also reduces cellular activity.
5HT1 receptors have the highest affinity for serotonin and so are therefore presumably the most active receptor type under normal conditions.
5HT1A seems to be important in affecting mood, as 5HT1A antagonists cause anxiety. Agonists (such as buspirone) have mild anxiolytic effects.
This in part seems to be due to inhibition of GABAergic neurones in the hippocampus (this inhibits inhibitory inputs, a process called DISINHIBITION) and causes an overall increase in hippocampal activity.
Also blocking amygdaloid activity which reduces anxiety.
Synapse. 2000 Dec 1;38(3):328-37
J. Neurosci. 1997 Jul 17(14) 5591-5598
5HT1 receptors also act as autoreceptors, inhibiting further serotonin release. It has been proposed that this is one of the reasons why SSRI antidepressants take about 2 weeks to have any theraputic effect is due to the time taken for the desensitisation of autorecepetors.
Riad et.al. J Neurosci. 2004 Jun 9;24(23):5420-6.
Acute treatment with the antidepressant fluoxetine internalizes 5-HT1A autoreceptors and reduces the in vivo binding of the PET radioligand [18F]MPPF in the nucleus raphe dorsalis of rat
I think this is going to get VERY long for a single post. So I'll continue in another one!
