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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 7 of 7. This is the beginning of the thread.
Posted by Kizzie2 on October 16, 2011, at 12:09:54
Hi - I just wondered if anyone can explain what any if this actually means. It's taken from CNS forum. I am long term ad user and trying to find out effects (paxil then anafranil). Thanks for any help x. CNS Image Bank:
Depression - Long term antidepressant treatmentThe consequences of long term antidepressant treatment
Chronic administration of antidepressants can cause a number of changes in the brain, depending on the particular drug type: (1) SSRIs and MAOIs desensitize inhibitory 5-HT1A somatodendritic receptors and inhibitory pre-synaptic 5-HT1D autoreceptors. They can also prevent the uptake of 5-HT into the nerve terminal by binding to the imipramine binding site (2) TCA, electroconvulsive therapy (ECT) and other non-SSRI antidepressants can sensitize inhibitory post-synaptic 5-HT1A receptors and can reduce the expression of stimulatory 5-HT2A receptors. (3) Experimental evidence suggests that chronic antidepressant treatment can also affect post-receptor signalling mechanisms, such as G-proteins.
Changes in gene expression following administration of antidepressants: noradrenaline transporter
Tricyclic antidepressants and selective noradrenaline re-uptake inhibitors rapidly bind to and block the action of noradrenaline re-uptake transporters (NARTs). Chronic administration of these antidepressants leads to changes in NART gene expression. A significant increase in NART expression is seen in the hippocampus and the in cingulate, frontal, parietal, perirhinal, entorhinal and insular cortices in response to chronic antidepressant treatment. A decrease in NART expression is seen in the temporal cortex.
Changes in gene expression following administration of antidepressants: serotonin transporter
Tricyclic antidepressants and selective serotonin re-uptake inhibitors rapidly bind to and block the action of serotonin re-uptake transporters (SERTs). Chronic administration of these types of antidepressants leads to changes in SERT gene expression. A significant increase in SERT expression is seen in the hippocampus and the cingulate, insular, perirhinal and parietal cortices in response to chronic antidepressant treatment.
The effects of chronic antidepressant treatment on gene expression in the brain
Although the acute action of antidepressant treatment is associated with monoamine re-uptake inhibition, the molecular adaptations underlying the therapeutic action of these agents have still to be determined. Chronic administration of desipramine, fluoxetine and tranylcypromine has been shown to up-regulate the cAMP signal transduction cascade resulting in increased expression and function of the transcription factor CRE binding protein (CREB), in various regions of the brain, particularly the cerebral cortex and hippocampus. In turn, enhanced CREB expression leads to an upregulation in cAMP response element (CRE )-mediated gene transcription in these areas. For example, brain-derived neurotrophic factor (BDNF) expression is increased in the hippocampus. Studies have also demonstrated that expression of other transcription factors (NGF1-A, mineralocorticoid receptor (MR), glucocorticoid receptor (GR), c-Fos) is increased following treatment with a similar range of antidepressant drugs. Decreases in mRNA of corticotrophin-releasing factor (CRF) and its receptor CRF-R1 have been detected in the hypothalamus and amygdala, respectively, following chronic amitriptyline administration. Moclobemide causes decreased expression of the transcription factor NGF1-B in the hippocampus.
Posted by Kizzie2 on October 16, 2011, at 12:54:28
In reply to Long term AD use effects, posted by Kizzie2 on October 16, 2011, at 12:09:54
Apologies - I meant to add the study below to my original question. I have tried to google some of the content but still struggling to work out what it *actually* means. The reason I am asking these questions is because I am now in my 13th year on AD's with no immediate prospect of being able to come off - although I have reduced the dose. I am very keen to find out if a/ there are long term effects I need to be concerned about and b/ whether there is anything I can do to minimise them with diet/healthy living/mindfulness/meditation (partic related to any brain or emotional impacts ). Thank you !! for any advice.
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Long-term clomipramine treatment upregulates forebrain acetylcholine muscarinic receptors, and reduces behavioural sensitivity to scopolamine in mice.AuthorsTsukagoshi H, et al. Show all Journal
J Pharm Pharmacol. 2000 Jan;52(1):87-92.Affiliation
Department of Anesthesiology and Reanimatology, Gunma University School of Medicine and Hospital, Maebashi, Japan.Abstract
We have investigated the effects of long-term treatment with clomipramine, a tricyclic antidepressant, on central muscarinic acetylcholine receptors (mAChR) in mice. Repeated clomipramine administration resulted in an increase in the forebrain receptor density value (Bmax) for [3H]quinuclidinyl benzilate, a muscarinic ligand (P < 0.05), that was dependent on dose per administration (saline or 5, 10, or 20 mg kg(-1) once a day for 7 days) and number of days treated (20 mg kg(-1) for 1, 3, 5, or 7 days). No change in apparent affinity (defined as the reciprocal of the dissociation constant) (KD) occurred. Seven daily treatments with clomipramine (saline or 5, 10, or 20 mg kg(-1)) reduced hyperlocomotion induced by scopolamine (0.5 mg kg(-1), s.c.) dose-dependently, and the effect of 20 mg kg(-1) clomipramine was significant (P < 0.05). These results suggest that an upregulation of mAChR is produced by repeated clomipramine administration, and such a change is responsible for the decreased sensitivity to the muscarinic antagonist scopolamine.
Posted by kizzie2 on October 17, 2011, at 3:57:33
In reply to Re: Long term AD use effects ((more info, posted by Kizzie2 on October 16, 2011, at 12:54:28
.
Posted by Phidippus on October 17, 2011, at 18:14:28
In reply to Long term AD use effects, posted by Kizzie2 on October 16, 2011, at 12:09:54
> Chronic administration of antidepressants can cause a number of changes in the brain, depending on the particular drug type: (1) SSRIs and MAOIs desensitize inhibitory 5-HT1A somatodendritic receptors and inhibitory pre-synaptic 5-HT1D autoreceptors. They can also prevent the uptake of 5-HT into the nerve terminal by binding to the imipramine binding site (2) TCA, electroconvulsive therapy (ECT) and other non-SSRI antidepressants can sensitize inhibitory post-synaptic 5-HT1A receptors and can reduce the expression of stimulatory 5-HT2A receptors. (3) Experimental evidence suggests that chronic antidepressant treatment can also affect post-receptor signalling mechanisms, such as G-proteins.
SSRIs and MAOIs desensitize some receptors. TCA, ECT and other antidepressants can sensitize some receptors while reducing other receptors. Antidepressant treatment can also affect the way receptors signal each other (whether this is good or bad is not weighed on here)
> Tricyclic antidepressants and selective noradrenaline re-uptake inhibitors rapidly bind to and block the action of noradrenaline re-uptake transporters (NARTs).
TCAs and SNRIs quickly bind to and block noradrenaline re-uptake transporters, making noradrenaline more abundant.
>Chronic administration of these antidepressants leads to changes in NART gene expression.
The process of gene expression is used by all known life to generate the macromolecular machinery for life Chronic administration of antidepressant alters this function in NART
>A significant increase in NART expression is seen in the hippocampus and the in cingulate, frontal, parietal, perirhinal, entorhinal and insular cortices in response to chronic antidepressant treatment.
several parts of the brain show increased NART expression
> A decrease in NART expression is seen in the temporal cortex.
NART expression is lower in the temporal area of the brain
> Tricyclic antidepressants and selective serotonin re-uptake inhibitors rapidly bind to and block the action of serotonin re-uptake transporters (SERTs). Chronic administration of these types of antidepressants leads to changes in SERT gene expression. A significant increase in SERT expression is seen in the hippocampus and the cingulate, insular, perirhinal and parietal cortices in response to chronic antidepressant treatment.Tricyclic antidepressants and selective serotonin re-uptake inhibitors rapidly bind to and block the action of serotonin re-uptake transporters. As with NARTs, SERT gene expression is affected and higher quantities SERT can be found in parts of the brain.
> Although the acute action of antidepressant treatment is associated with monoamine re-uptake inhibition, the molecular adaptations underlying the therapeutic action of these agents have still to be determined. Chronic administration of desipramine, fluoxetine and tranylcypromine has been shown to up-regulate the cAMP signal transduction cascade resulting in increased expression and function of the transcription factor CRE binding protein (CREB), in various regions of the brain, particularly the cerebral cortex and hippocampus. In turn, enhanced CREB expression leads to an upregulation in cAMP response element (CRE )-mediated gene transcription in these areas. For example, brain-derived neurotrophic factor (BDNF) expression is increased in the hippocampus. Studies have also demonstrated that expression of other transcription factors (NGF1-A, mineralocorticoid receptor (MR), glucocorticoid receptor (GR), c-Fos) is increased following treatment with a similar range of antidepressant drugs. Decreases in mRNA of corticotrophin-releasing factor (CRF) and its receptor CRF-R1 have been detected in the hypothalamus and amygdala, respectively, following chronic amitriptyline administration. Moclobemide causes decreased expression of the transcription factor NGF1-B in the hippocampus.
this just talks about elevations in neurotransmitters in the brain and decreases.nothing in this article points to whether these changes are good or bad, it just points out the effects of certain drugs on the brain
Posted by kizzie2 on October 18, 2011, at 5:28:54
In reply to Re: Long term AD use effects » Kizzie2, posted by Phidippus on October 17, 2011, at 18:14:28
Hi - thank you so much for replying :-)
Does anyone have any other thoughts on the actual impacts of these changes ....
Also a bit more info re NART & SERT expression - what these mean - and what are their implications.
Thanks again - im always staggered by the amount of knowledge on this board.
Posted by kizzie2 on October 19, 2011, at 10:49:06
In reply to Re: Long term AD use effects, posted by kizzie2 on October 18, 2011, at 5:28:54
.
Posted by huxley on October 25, 2011, at 2:32:06
In reply to Re: Long term AD use effects BUMP, posted by kizzie2 on October 19, 2011, at 10:49:06
I too would like an explanation.
Most people here dont want to know/believe things that are negative about meds.
This is the end of the thread.
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