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
poster:Phidippus
thread:999894
URL: http://www.dr-bob.org/babble/20111016/msgs/1000034.html