Posted by linkadge on May 8, 2010, at 20:39:19
In reply to Re: Questions about tricyclics???, posted by SLS on May 8, 2010, at 20:08:45
First off the whole 5-ht1a autoreceptor level depression link is a bunch of bunk IMHO. I have read dozens of studies on whether serotonin 1a autoreceptor are overactive or underactive in depression. Nothing seems conclusive. Perhaps the antidepressant effect of SSRI's is dependant upon the activity of 5-ht1a autreceptors, but not drugs like NRI's or other atypical antidepressants (?). Running acutally increase the responsivity of 5-h1a autoreceptors, yet is a clinically effective antidepressant strategy.
>I'm trying to figure out why 5-HT1a receptor >knock-out mice demonstrate increased anxiety. My >mind is mush. Also, people with SA have reduced >numbers of 5-HT1a receptors, particularly in the >amygdala as determined by PET scans.
It totally depends on whether this is pre or post synaptic.
>Are these receptors normally inhibitory or >excitatory? I would guess that they would be >inhibitory if they are heteroreceptors.
Post synaptic 5-ht1a receptors are typically inhibitory but other receptors (ie 5-ht2) are excitory. Activating presynaptic receptors would reduce overall serotonergic neurotransmission (in certain brain regions) and hence decrease post synaptic activity at all serotonin receptor subtypes. Serotonin (in hippocapal regions) is typically anxiolytic, but this is more controlled by 5-ht1b autoreceptors. In the DRN it is anxiogenic.
>It is interesting that 5-HT1a receptor partial >agonists are proposed as efficacious in treating >anxiety disorders - and perhaps depression.Serotonergic firing in the DRN can be highly anxiogenic. On the other hand increased firing of the DRN may be associated with antidepressant effect. Drugs like buspar and nicotine decrease (or regulate?) DRN firing wherase drugs like pindolol increase it. The former is associated with reducing anxiety and the latter with reducing depression.
Anyhow, I *highly doubt* that serotonin is the only neurotransmitter implicated in social anxiety. After all, drugs like Nardil and Clonazepam are the gold standard for SAD. Nardil is not selective to serotonin and both agents have strong gabaergic effect. Gabapentin also shows anti-SAD effects and is not a reuptake inhibitor. I would think that this implicates GABA more than serotonin in SAD.
Dopamine, somostatin, oxytocin, CCK, gaba, substance p, 5-ht2, enkaphalin, PEA, etc etc. have also been implicated in SAD at one point or another.
The problem is that SAD is a post SSRI disorder. Just because the TCA's were not typically used in SAD does not mean they are not effective.
Some studies suggest that inhibiting noradrenergic reuptake increases impaired social functioning (in depression) more than serotonin reuptake inhibition. I would think that the TCAs are probably highly efficatious in SAD.
Linkadge
poster:linkadge
thread:946012
URL: http://www.dr-bob.org/babble/20100504/msgs/946807.html