? on drugs and DA/NE/5-HT reuptake

Fernando Boix fboix at pons.uio.no
Sun Aug 13 09:33:24 EST 1995

waynerad at oz.net (Wayne Radinsky) wrote:

>Hello all,

>Cocaine inhibits dopamine and norepinephrine reuptake.  Prozac (fluoxetine)
>inhibits serotonin reuptake.  Over time, cocaine causes serious depletion
>of dopamine and norepinephrine, because they get released and metabolized
>instead of released and re-taken-up.  Prozac, on the other hand, apparently
>does not cause depletion of serotonin over time.  Why?  Dopamine, 
>norepinephrine, and serotonin are all low-molecular-weight biogenic
>amine neurotransmitters and blocking reuptake ought to (it seems to me)
>affect them all in basically the same way.

>I figure this is either a simple question with a complex answer, or there
>is something really obvious that I've overlooked.  Since this is my first
>post to bionet.neuroscience, I hope this question isn't too silly ;-).


Cocaine does not causes serious dopamine depletion, and not by the
reason you mention. In the dopamine synapse, recently synthesized
dopamine is preferentially released. Reuptaked dopamine is stored and
released only if there is a big demand and the stores of recently
synthesized dopamine are depleted (it will be released only as "last"
measure). Cocaine can reduce the synthesis of dopamine, and therefore
reduce the stores of newly synthesized dopamine, because by inhibiting
reuptake it increases the dopamine concentration in the synaptic
cleft, increasing the action of dopamine on D2 autoreceptors which
their activation inhibits dopamine synthesis. You can see, the thing
is no so easy and straightforward as it seems, and you recognise in
your post.

Fernando Boix
Dept. of Neurophysiology
University of Oslo

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