Posted by SLS on May 20, 2009, at 5:44:34
In reply to Re: Do SSRI's cause dopamine depletion » Alexanderfromdenmark, posted by sowhysosad on April 26, 2009, at 22:30:20
> > Also I think there's a difference between acute admnistration and long term adminitstration. Fx the brain in reponse to the huge increase in serotonin made say "F*ck man, lets pump out some dopamine to balance things out", so you get an increase dopamine, then you take an SSRI again and the brain again says "F*ck it man, keep that dopamine going, pump it up!", then after a period of weeks or months "The adujustment period", the brain just says"f*ck it, no more, we'll just get used to all that f*ck*ng serotonin and stop pumpting the dopamine" and that's when stuff like SSRI apathy, fatigue and PSSD complications set in.
>
> You could be right. Weirdly though, SSRI's can also increase dopamine through other mechanisms. As I understand it, the dopamine reuptake pump starts to soak up some of that excess serotonin floating around, thus preventing reuptake of dopamine and leaving more in the synapse. Maybe that's how fluoxetine boosts dopamine in some parts of the brain?
Don't forget circuitry.I think it has more to do with serotoninergic pathways modulating dopaminergic neurotransmission downstream. Perhaps there is a dysinhibition of dopamine activity as specific 5-HT receptors downregulate as a result of chronic exposure to SRI drugs like fluoxetine. Fluoxetine is a strange drug that is often considered to be an atypical SSRI. It does more than just inhibit the reuptake of serotonin.
- Scott
*********************************************Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex
by
Bymaster FP, Zhang W, Carter PA,
Shaw J, Chernet E, Phebus L, Wong DT, Perry KW.
Neuroscience Research Division,
Lilly Research Laboratories,
Lilly Corporate Center, Indianapolis, IN 46285-0510, USA.
[email protected]
Psychopharmacology (Berl) 2002 Apr;160(4):353-61ABSTRACT
RATIONALE: The selective serotonin uptake inhibitor (SSRI) fluoxetine has been shown to not only increase the extracellular concentrations of serotonin, but also dopamine and norepinephrine extracellular concentrations in rat prefrontal cortex. The effect of other SSRIs on monoamine concentrations in prefrontal cortex has not been thoroughly studied. OBJECTIVE: The aim of this study was to compare the ability of five systemically administered selective serotonin uptake inhibitors to increase acutely the extracellular concentrations of serotonin, norepinephrine and dopamine in rat prefrontal cortex. METHODS: The extracellular concentrations of monoamines were determined in the prefrontal cortex of conscious rats using the microdialysis technique. RESULTS: Fluoxetine, citalopram, fluvoxamine, paroxetine and sertraline similarly increased the extracellular concentrations of serotonin from 2- to 4-fold above baseline. However, only fluoxetine produced robust and sustained increases in extracellular concentrations of norepinephrine and dopamine after acute systemic administration. Fluoxetine at the same dose blocked ex vivo binding to the serotonin transporter, but not the norepinephrine transporter, suggesting that the increase of catecholamines was not due to non-selective blockade of norepinephrine uptake. Prefrontal cortex extracellular concentrations of fluoxetine at the dose that increased extracellular monoamines were 242 nM, a concentration sufficient to block 5-HT(2C) receptors which is a potential mechanism for the fluoxetine-induced increase in catecholamines. CONCLUSION: Amongst the SSRIs examined, only fluoxetine acutely increases extracellular concentrations of norepinephrine and dopamine as well as serotonin in prefrontal cortex, suggesting that fluoxetine is an atypical SSRI.
poster:SLS
thread:883495
URL: http://www.dr-bob.org/babble/neuro/20090129/msgs/896762.html