Posted by PhoenixGirl on February 1, 2001, at 12:33:16
In reply to Re: But how is that beneficial? » PhoenixGirl, posted by Sunnely on January 31, 2001, at 19:27:38
Ok, I sort-of get that. If that hypothesis is true, then how is the brain affected when ADs are stopped? I'm trying to figure out if it's possible for ADs to actually bring on more depression when they are stopped.
> Hi PhoenixGirl,
>
> If the explanation I posted earlier got you more confused, you're probably not alone. Indeed it seems illogical that the down regulation of receptors (e.g., serotonin) would correlate with the onset of antidepressant action. But this is exactly the core of the HYPOTHESIS which states that changes in neurotransmitter receptor sensitivity may actually mediate clinical effects of antidepressant drugs.
>
> This antidepressant action is based on the "Monoamine Hypothesis of Depression," which simply states that depression is due to a deficiency in one or another of three biogenic monoamines, namely serotonin, norepinephrine (noradrenaline) and/or dopamine.
>
> During "normal state" i.e., no depression, all the regulatory elements of the neuron are also normal: namely, the enzyme monoamine oxidase (MAO) which destroys the neurotransmitter; the monoamine reuptake pump which terminates the action of the neurotransmitter by sweeping it out of the synapse; and the postsynaptic receptors which react to the release of neurotransmitter.
>
> In state of depression, the monoamine neurotransmitter is depleted, causing neurotransmitter deficiency. The consequences of monoamine neurotransmitter depletion is that the postsynaptic receptors abnormally upregulate (increased in number). This upregulation correlates with the production of the depressive illness, and is HYPOTHETICALLY linked to the cause of depression. The consequence of long-lasting blockade of MAO or monoamine oxidase by monoamine oxidase inhibitors (MAOIs) such as Nardil, Parnate, Marplan, or via reuptake inhibition such as the SSRIs or tricyclic antidepressants, is for the neurotransmitter receptors to down regulate. This state of neurotransmitter down regulation correlates with the onset of antidepressant action. This period usually takes 2-3 weeks ("lag time" of antidepressant action).
>
> In sum, the monoamine neurotransmitter receptors are "upregulated" in state of depression, whereas antidepressants causes them to "down regulate."
>
> I hope this clears up the confusion, somehow.
>
> ================================================
>
> > I don't understand how a reduction in the number of neurotransmitter receptors could help depression. Seems like it would make it worse? Or else, it seems like if you stopped the AD, and the number of receptors was still low, you would be more depressed than before you started the drug. That would make it so that you would have to stay on the drug to keep from becoming more depressed.
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URL: http://www.dr-bob.org/babble/20010131/msgs/53108.html