Posted by linkadge on February 7, 2009, at 17:43:27
In reply to Re: SSRI Induced HPTA Disruption, posted by SLS on February 7, 2009, at 13:31:58
SSRI's tend to increase the respsivness of dopamine d3 receptors. 3 week treatemtns with SSRI's, TCA's and ECT increase d3 receptor mRNA in certain limbic brain regions. Whether this is (as some suggest) a common target of antidepressive agents or simply an upregulation in responce to decrease dopaminergic function is unknown.
If the d3 receptors are a common target of AD agents, then perhaps mirapex's AD effect is a result of its potent d3 receptor agonism. It may be, as you suggest, that repeated exposure leads to desensiziaton and thus loss of clinical effect. Perhaps SSRI's can compensate by upregulating the receptors. BDNF is known to regulate the expression of the d3 receptors. Injections of BDNF may exert their AD effect by increaseing the responsivity of the d3 receptors. There is also the possibility that AD's increase d3 receptor expression by increasing BDNF levels and not by a dopamine supersensitivity responce to a serotonin boost.
A futher point of interest is this. As I mentioned in a previous post, certain AD agents (such as NMDA antagonists) don't increase BDNF levels. But it is interesting to note that NMDA antagonists work to functionally agonize d3 receptors. Infact, all of the behavioral effects of high dose NDMA antagonists can be blocked selectively by d3 receptor antagonists.
In other words, NMDA antagonists might exert their rapid acting AD effects by directly activating d3 receptor systems, wherease conventional AD agnets work by upregulating d3 receptor expression via BDNF enhancement.
Certain NMDA antagonists like zinc, also increase BDNF. Adding zinc to subtheraputic doses of TCA's produces AD effects in animals.
Linkadge
poster:linkadge
thread:878296
URL: http://www.dr-bob.org/babble/20090203/msgs/878796.html