Posted by robot on November 14, 2004, at 20:03:14
In reply to Re: Long-standing Anhedonia, posted by Shalom34Israel on November 13, 2004, at 14:29:05
"Many drugs are relatively selective for one of the monoaminergic systems—for example, serotonin for the SSRIs and norepinephrine for reboxetine and desipramine. However, before we assume that these agents are truly selective, it is important to keep in mind that there is considerable co-localization and "cross-talk" of monoamines in the central nervous system (54). That is, monoamines are mutually regulating. Norepinephrine itself as well as norepinephrine selective reuptake inhibitors (NSRIs) enhance the release of both dopamine and serotonin in the forebrain (55).
The effect of NSRIs on serotonin and dopamine may be explained by the observation that norepinephrine, acting through alpha1 receptors, can induce release of these transmitters (54). However, in addition, the norepinephrine transporter protein—the reuptake site—also has high affinity for the reuptake of dopamine (56). Thus NSRIs are, in effect, dopamine reuptake inhibitors as well. This concept is supported by Karson's finding (57) that spontaneous blink rates—as noted, a putative measure of forebrain dopamine activity—were elevated among depressed patients who were taking tricyclic antidepressants. Thus enhancement of norepinephrine transmission—by reuptake blockade or by a reduction in the metabolism of norepinephrine by inhibition of monoamine oxidase—would be expected to induce an enhancement of arousal via the norepinephrine mechanisms (58) but also to enhance reward acquisition—that is, motivation—through actions on dopaminergic systems.
The interplay of serotonin with norepinephrine and dopamine is more complicated because of the complexity of the serotonin receptor system relative to the catecholamines. For example, serotonin has been shown to both enhance and inhibit dopaminergic activity in the frontal cortex and nucleus accumbens, depending on the type of serotonin receptor subtype that is activated (21). The inhibition of dopamine by serotonin—primarily via 5-HT2C receptors (59,60,61)—may explain why highly selective SSRIs have been shown to reduce dopamine release in the frontal cortex or nucleus accumbens (62,63) and reward acquisition in animals (64,65,66).
This effect may parallel the mood-flattening effect of these agents among some patients and is consistent with the concept of a link between serotonin and constraint of dopaminergic systems as posited by Depue and colleagues (40). Clinically, it is important to keep in mind that not all patients who are treated with SSRIs will experience a flattening effect. However, it has been our observation that when a therapeutic failure occurs with one of these agents, it is often the result of a lack of improvement in the anhedonia experienced by many depressed patients."
> > I seem to have chronic mild depression which anti-depressants do little to change. But I believe now that a more basic anhedonic tendency is the real problem. I have been anhedonic as long as I can remember.
> > Does anyone have any treatment suggestions. I am currently taking 20mg of Lexapro and it did give me more energy. But I still am unable to enjoy myself and feel good.
> anhedonia is relieved more by dopaminergic medications than serotonin drugs. But if you have been that way as long as you can remember, treatment maybe difficult.