Posted by SLS on April 21, 2006, at 14:20:15
In reply to interesting- re clonazepam and 5-HT transporter, posted by zeugma on April 20, 2006, at 20:08:27
I would be interested to know what are the acute direct effects of clonazepam on the 5-HT system. So many people find it depressogenic almost immediately. I found this to be true of me.
Also, increasing the number of 5-HT1a postsynaptic receptors in the hippocampus might actually produce memory impairments. I believe they are inhibitory rather than excitatory. They hyperpolarize the membrane.http://www.nirs.go.jp/report/nene/h14/04/65.html
What I find weird is that chronic exposure to various classes of antidepressants increases the disinhibitory response to 5-HT1a antagonists. I guess there must be some sort of accomodation downstream to balance out the increased number of receptors so as to make them less sensitive to activation by serotonin. If the excitatory postsynaptic receptors remain unchanged, the net effect should be an enhanced signal-to-noise ratio, despite the increased synaptic serotonin that results from SERT inhibition. This should result in the enhancement of serotonergic neurotranmission. Thus we have a possible explanation for the production of a serotonergic antidepressant response.
http://www.biopsychiatry.com/5ht1a.htm
At the moment this makes sense to me. In five minutes I guarantee I'll be confused again!
- Scott
> I found this article on how clonazepam upregulates the serotonin transporter:
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> Neuropharmacology. 1995 Oct;34(10):1327-33.
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> Serotonin turnover rate, [3H]paroxetine binding sites, and 5-HT1A receptors in the hippocampus of rats subchronically treated with clonazepam.
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> Lima L, Trejo E, Urbina M.
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> Laboratorio de Neuroquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas, Venezuela.
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> Selective central benzodiazepine agonists, such as clonazepam, are known to modify serotonin and 5-hydroxyindoleacetic content in the brain. In order to further study the effect of this benzodiazepine on serotonin turnover rate, rats received clonazepam, 10 mg/kg for 10 days, and the concentrations of serotonin and 5-hydroxyindoleacetic acid were determined in the hippocampus after inhibition of monoamineoxidase with pargyline. The results indicate a reduction in the turnover rate of the monoamine. In addition, the systemic administration of clonazepam produced a decrease in the Bmax of [3H]DPAT binding to 5-HT1A sites in the hippocampus. By contrast, this effect was not observed if clonazepam was delivered into the dorsal raphe nucleus by osmotic minipumps. The binding of [3H]paroxetine to 5-HT reuptake sites was increased by the treatment with clonazepam. The present observations indicate that clonazepam produces a reduction of serotonin turnover rate in the hippocampus of the rat concomitant with a down-regulation of 5-HT1A binding sites, probably by an effect at the forebrain projections. There is also an up-regulation of the serotonin transporter, which might contribute to a reduction in the synaptic availability of serotonin during clonazepam treatment.
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8570030&query_hl=98&itool=pubmed_docsum
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> This might make clonazepam an option similar to tianeptine in its effect on the 5-HT transporter. And it is consonant with the idea that the s/s genotype is prone to anxiety/stress.
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> -z
poster:SLS
thread:629584
URL: http://www.dr-bob.org/babble/20060417/msgs/635570.html