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Re: emotion and movement and motivation » KaraS

Posted by Sad Panda on August 5, 2004, at 23:29:25

In reply to Re: emotion and movement and motivation » zeugma, posted by KaraS on August 4, 2004, at 16:29:32

> > This is a passage from a book, "Synaptic Self", that devotes a whole chapter to the topic of motivation:
> >
> > "the nucleus accumbens sits at the crossroads of emotion and movement, and... dopamine release in this region plays a crucial role in motivated or goal-directed behavior. This conclusion was based on four main sets of observations. First, the nucleus accumbens receives massive dopamine inputs from the tegmentum. Second, injection of methamphetamine or cocaine into the nucleus accumbens leads to behavioral activation: animals start exploring their environment as if in search of something. Third, the accumbens sends output to areas involved to areas involved in the control of movement (such as the pallidum, an area that connects with the movement-control regions in the cortex and brain stem). Today, it is widely accepted that the nucleus accumbens and areas with which it is connected constitute key elements of a circuit through which emotional stimuli direct behavior toward goals." [p.247]
> >
> > A couple of comments. The author mentions that the brain stem is involved in movement control. This might explain why nortriptyline helped me more with the 'intention-motivation' linkage than Stattera, because as my pdoc and the Lilly Corp. said, TCA's work more in the brainstem, while Strat is selective for the prefrontal cortex. The PFC has been the presumed site of the dysfunctions involved in ADD/ADHD (see for example "The Executive Brain"). I would say that the PFC is closely involved with cloudy/unclear thinking, but according to the diagram on p. 248 of "Synaptic Self", the PFC is only remotely connected to the motor system, via a GABA inhibitory pathway to the nucleus accumbens, and thence via another GABA pathway to the pallidum. The ventral tegmental area sends DA pathways to both the nucleus accumbens and to the pallidum. So it much more closely involved in motor control than the PFC. Strattera made my mind perfectly clear, but did not enhance control of movements.
> >
> > Also, the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues. In the 1960's, with the clinical success of the TCA's and MAOI's, norepinephrine was thought to be crucial to AD response as all these drugs enhanced NE transmission while many did nothing for 5-HT. So NE was extensively researched, but of course by using '60's technology, which is nothing compared to what we have now. Then about 1990 the SSRI's became the official 'antidepressants' of choice. So 5-HT became the transmitter of interest, and of course technical advances made 5-HT studies a lot more informative than those studies made while NE was the topic of choice. Now with CYMBALTA finally released we will no doubt see an explosion of studies on NE in mood disorders.
> >
> > In terms of understanding the relative roles of norepinephrine and dopamine in pathophysiology, the most detailed examination I know of has been in the field of narcolepsy, where DA vs. NE- ergic drugs were compared using EEG studies on narcoleptic dogs. The upshot was that DA reuptake inhibitors enhanced wakefulness, while NE reuptake inhibitors had no effect on wakefulness but selectively blocked REM sleep:
> >
> > http://www.sro.org/pdf/863.pdf
> >
> > This result is interesting, because premature induction of REM has always been linked to the melancholic subtype of depression. I do hope CYMBALTA lives up to the symmetry implied in its name, and promotes greater understanding of the 'other' neurotransmitter involved in psychopathology. You know how I feel about misreaders of PubMed abstracts ;), so I would be remiss if I did not point out that the esteemed author whose diagrams and text I drew on above can make shocking misstatements such as this:
> >
> > "These [SSRI's] are as effective as tricyclics in helping people, but probably not more so. This is to be expected, since both classes of drugs basically do the same thing- make more serotonin available at synapses. But the SSRI's do the job with fewer side effects- they are selective for serotonin, so the side effects caused by enhancing norepinephrine are eliminated." [p. 275]
> >
> > This explains why it is hard to say exactly what NE's role is in a range of disorders. The author is a leading researcher in the field of neuroscience.
>
>
> Thanks so much Zeugma!!!
>
> It has been very helpful to get the textbook answer along with how that translates to your personal experience. I feel like I have more of the full picture.
>
> You wrote: "the author (writing in 2002) seriously downplays the role of norepinephrine in mood disorders as well as in other crucial finctions, such as the motivation issues." I can see someone questionning the role of NE in motivation but as an antidepressant? Wouldn't the success rate of the noradrenergic TCAs alone prove that statement false?
>
> As for that shocking misstatement, I can't believe that the author meant it to read like that. Not only does it say something really silly and wrong, but the argument supporting it doesn't make any sense. This "expert" needs to get another editor!
>
> -K
>
>

I think he is very wrong too. The TCA's that have higher efficacy than SSRI's, Clomipramine, Amitriptyline & Imipramine, have widely varying degrees of serotonin reuptake inhibition, but are all fairly equal & potent NE reuptake inhibitors. Initially, they are only mild NRI's, but after their first stage of metabolism, they become desmethy-Clomipramine, Nortriptyline & Desipramine which are all potent NRI's but have practically no power at all as an SRI. Also, these metabolites have longer half lives which further swings the balance in favour of NE.

Cheers,
Panda.



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