Posted by myco on April 3, 2009, at 10:33:49
In reply to How come no MAOI/TCA poop out? Only SSRI poop out, posted by NewQuestions on April 3, 2009, at 10:11:01
> It seems like poop out is a SSRI phenomenon only. It does not seem like long time users of MAOIs and TCAs poop out. Why?
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Maois do "poop out" but not how you may think. It's not that stop working really...well studies suggest they do in a way. For me im over 4 months now on nardil and the physical aspect of it is gone...it has incorporated itself into my behaviours now only...no other indication im on the med. but im noticing over time that my concentration and energy levels, that it once was awesome for, are going down (still good on anxiety though)...this is attributable to Dopamine downregulation or inhibition/dulling of dopamine "firing"...this happens for most AD's after awhile. they begin to lose that DA and NE effect from downregulation of dopamine but normally retain the SE effect, if you have a need for it. those that experience "poop out" may simply neeed more DA and NE perhaps not as much SE. I dont like ssri's....depression and anxiety are so much more than just seratonin.
2 relevent studies (i have full text if needed):
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"Association of Changes in Norepinephrine and Serotonin Transporter Expression with the Long-Term Behavioral Effects of Antidepressant Drugs"Zhao et al. Neuropsychopharmacology (2008), 115
Previous work has shown that repeated desipramine treatment causes downregulation of the norepinephrine transporter (NET) and persistent antidepressant-like effects on behavior, ie effects observed 2 days after discontinuation of drug treatment when acute effects are minimized. The present study examined whether this mechanism generalizes to other antidepressants and also is evident for the serotonin transporter (SERT). Treatment of rats for 14 days with 20 mg/kg per day protriptyline or 7.5 mg/kg per day sertraline reduced NET and SERT expression, respectively, in cerebral cortex and hippocampus; these treatments also induced a persistent antidepressantlike
effect on forced-swim behavior. Increased serotonergic neurotransmission likely mediated the behavioral effect of sertraline, as it was
blocked by inhibition of serotonin synthesis with p-chlorophenylalanine; a parallel effect was observed previously for desipramine and
noradrenergic neurotransmission. Treatment with 20 mg/kg per day reboxetine for 42, but not 14, days reduced NET expression; antidepressant-like effects on behavior were observed for both treatment durations. Treatment for 14 days with 70 mg/kg per day venlafaxine, which inhibits both the NET and SERT, or 10 mg/kg per day phenelzine, a monoamine oxidase inhibitor, produced
antidepressant-like effects on behavior without altering NET or SERT expression. For all drugs tested, reductions of NET and SERT
protein were not accompanied by reduced NET or SERT mRNA in locus coeruleus or dorsal raphe nucleus, respectively. Overall, the
present results suggest an important, though not universal, role for NET and SERT regulation in the long-term behavioral effects of
antidepressants. Understanding the mechanisms underlying transporter regulation in vivo may suggest novel targets for the development
of antidepressant drugs
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"Long-term administration of monoamine
oxidase inhibitors alters the firing rate and
pattern of dopamine neurons in the ventral
tegmental area"Chenu et al. International Journal of Neuropsychopharmacology, Page 1 of 11.
Monoamine oxidase inhibitors (MAOIs) exert their antidepressant action by increasing the function of the serotonin (5-HT), norepinephrine and dopamine (DA) systems. There is, however, limited electrophysiological data on the effects of MAOIs on DA neurons. The effects of 2-d and 21-d administration of three MAOIs were investigated (clorgyline, selective MAOI-A; deprenyl, selective MAOI-B; phenelzine, non-selective MAOI) on the firing activity of DA neurons in the ventral tegmental area using in-vivo
electrophysiology in rats. Short-term clorgyline (1 mg/kg) and phenelzine (2.5 mg/kg) was devoid of
effect on DA neurons, whereas prolonged administration significantly decreased their firing rate (by 30% and 20%, respectively), number of bursts (by 80% and 45%, respectively), and percentage of spikes occurring in bursts only in clorgyline-treated rats (70 %). Deprenyl (0.25 mg/kg) was without effects. DA firing was restored in clorgyline-treated rats by inhibiting 5-HT synthesis using para-chlorophenylalanine
(p-CPA; 300 mg/kg . d for three consecutive days). The 5-HT3 antagonist ondansetron (0.5 mg/kg) was devoid of effect in control rats, but completely reversed the alterations of DA neuronal activity in clorgyline-treated rats. An attenuation of DA neuronal activity was thus produced by prolonged blockade of MAOA activity. The absence of effect of MAOA inhibition after subacute administration suggested an indirect mechanism. This was confirmed by the observation that p-CPA antagonized the effects of clorgyline.
Since ondansetron completely reversed the effects of clorgyline on DA neuronal activity, the effects
of MAOA inhibition appeared to be mediated by 5-HT3 receptors.
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poster:myco
thread:888474
URL: http://www.dr-bob.org/babble/20090330/msgs/888480.html