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Kobayashi, 2012 Chronic fluoxetine selectively upregulates dopamine D₁-like receptors in the hippocampus.


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A very optimistic interpretation of neurological dysregulation.

 

Neuropsychopharmacology. 2012 May;37(6):1500-8. doi: 10.1038/npp.2011.335. Epub 2012 Jan 25.

Chronic fluoxetine selectively upregulates dopamine D₁-like receptors in the hippocampus.

Kobayashi K, Haneda E, Higuchi M, Suhara T, Suzuki H.

 

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Department of Pharmacology, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo, Japan. kkatsu-tky@umin.ac.jp

Abstract http://www.ncbi.nlm.nih.gov/pubmed/22278095

 

The dentate gyrus of the hippocampus has been implicated in mechanisms of action of selective serotonin reuptake inhibitors (SSRIs). We have recently demonstrated that the SSRI fluoxetine can reverse the state of maturation of the adult dentate granule cells and enhances serotonin 5-HT₄ receptor-mediated synaptic potentiation at the synapses formed by their mossy fiber axons. Here, we show that fluoxetine can induce long-lasting enhancement of dopaminergic modulation at the mossy fiber synapse. Synaptic responses arising from the mossy fiber-CA3 pyramidal cell synapse were recorded using acute mouse hippocampal slices. Dopamine potentiates mossy fiber synaptic transmission by activating D₁-like receptors. Chronic fluoxetine treatment induced a prominent increase in the magnitude of dopamine-induced synaptic potentiation, and this effect was maintained at least up to 1 month after withdrawal of fluoxetine. Quantitative autoradiography revealed that binding of the D₁-like receptor ligand [³H]SCH23390 was selectively increased in the dentate gyrus and along the mossy fiber in fluoxetine-treated mice. However, binding of the 5-HT₄ receptor ligand [³H]GR113808 was not significantly changed. These results suggest that chronic fluoxetine enhanced the dopaminergic modulation at least in part by upregulating expression of D₁-like receptors, while the enhanced serotonergic modulation may be mediated by modifications of downstream signaling pathways. These enhanced monoaminergic modulations would greatly increase excitatory drive to the hippocampal circuit through the dentate gyrus. The highly localized upregulation of D₁-like receptors further supports the importance of the dentate gyrus in the mechanism of action of SSRIs.

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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Wow! That is a very scientific document. I tend to be a "scanner" due to so many interests, so little time. But I did scan twices. Anyone able to give a one sentence, short interpretation in common lingo. :lol:

I think! Too much!

Jan. 2009 150 mg. Venlafaxine

2012

5 June 112.5 mg. Venflx

25 June 75 mg. Venflx

8 July Fluox 5ML (0 Venflx)[/b]

10 July aprox. 20 mg Fluoxetine liquid, trouble measuring between 4 - 5 ml, 0 Venflx.

15 July Fluox 5 ML + Vnflx. 10 - 6 grains

24 July Fluox 5ML + 37.5 mg Venflx.

10 Aug Fluox 4.5 ML

13 Aug.Fluox 18 mg liquid; 18 Aug. Fluox 17 mg; 25 Aug. Fluox 16 mg;

2 Sept Fluox 15 mg; 10 Sept Fluox 14 mg; 17 Sept. Fluox 13.6 mg; 29 Sept. Fluox 13 mg.

7 Oct. Fluox 12 mg; 14 Oct. Fluox 11 mg; 21 Oct; Fluox 10 mg; 23 Oct. 9mg; 26 Oct. 8 mg.

21 Nov. 5 mg; 3 Nov. ZERO

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"Fluoxetine actually f**s up your brain in another way we didn't even know about before. And also f**s it up worse than we thought in a way that we did know about. But it's okay, we're sure it's an improvement. We're sure that your f**d up brain is the healthy and optimal way for a brain to be, because we want to keep getting research funds so we can pay our rent, and all those funds come from pharmaceutical companies."

 

It's more than one sentence but I think it's a good summary.

Started on Prozac and Xanax in 1992 for PTSD after an assault. One drug led to more, the usual story. Got sicker and sicker, but believed I needed the drugs for my "underlying disease". Long story...lost everything. Life savings, home, physical and mental health, relationships, friendships, ability to work, everything. Amitryptiline, Prozac, bupropion, buspirone, flurazepam, diazepam, alprazolam, Paxil, citalopram, lamotrigine, gabapentin...probably more I've forgotten. 

Started multidrug taper in Feb 2010.  Doing a very slow microtaper, down to low doses now and feeling SO much better, getting my old personality and my brain back! Able to work full time, have a full social life, and cope with stress better than ever. Not perfect, but much better. After 23 lost years. Big Pharma has a lot to answer for. And "medicine for profit" is just not a great idea.

 

Feb 15 2010:  300 mg Neurontin  200 Lamictal   10 Celexa      0.65 Xanax   and 5 mg Ambien 

Feb 10 2014:   62 Lamictal    1.1 Celexa         0.135 Xanax    1.8 Valium

Feb 10 2015:   50 Lamictal      0.875 Celexa    0.11 Xanax      1.5 Valium

Feb 15 2016:   47.5 Lamictal   0.75 Celexa      0.0875 Xanax    1.42 Valium    

2/12/20             12                       0.045               0.007                   1 

May 2021            7                       0.01                  0.0037                1

Feb 2022            6                      0!!!                     0.00167               0.98                2.5 mg Ambien

Oct 2022       4.5 mg Lamictal    (off Celexa, off Xanax)   0.95 Valium    Ambien, 1/4 to 1/2 of a 5 mg tablet 

 

I'm not a doctor. Any advice I give is just my civilian opinion.

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"Fluoxetine actually f**s up your brain in another way we didn't even know about before. And also f**s it up worse than we thought in a way that we did know about. But it's okay, we're sure it's an improvement. We're sure that your f**d up brain is the healthy and optimal way for a brain to be, because we want to keep getting research funds so we can pay our rent, and all those funds come from pharmaceutical companies."

 

It's more than one sentence but I think it's a good summary.

 

The summary's good but certain bits seem to be missing some *'s ... lol

"Well my ship's been split to splinters and it's sinking fast
I'm drowning in the poison, got no future, got no past
But my heart is not weary, it's light and it's free
I've got nothing but affection for all those who sailed with me.

Everybody's moving, if they ain't already there
Everybody's got to move somewhere
Stick with me baby, stick with me anyhow
Things should start to get interesting right about now."

- Zimmerman

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WOW

 

Thanks for the vivid and clearer explanation. I can hardly wait to be f**n off of it - 17 mg's to go! :lol:

I think! Too much!

Jan. 2009 150 mg. Venlafaxine

2012

5 June 112.5 mg. Venflx

25 June 75 mg. Venflx

8 July Fluox 5ML (0 Venflx)[/b]

10 July aprox. 20 mg Fluoxetine liquid, trouble measuring between 4 - 5 ml, 0 Venflx.

15 July Fluox 5 ML + Vnflx. 10 - 6 grains

24 July Fluox 5ML + 37.5 mg Venflx.

10 Aug Fluox 4.5 ML

13 Aug.Fluox 18 mg liquid; 18 Aug. Fluox 17 mg; 25 Aug. Fluox 16 mg;

2 Sept Fluox 15 mg; 10 Sept Fluox 14 mg; 17 Sept. Fluox 13.6 mg; 29 Sept. Fluox 13 mg.

7 Oct. Fluox 12 mg; 14 Oct. Fluox 11 mg; 21 Oct; Fluox 10 mg; 23 Oct. 9mg; 26 Oct. 8 mg.

21 Nov. 5 mg; 3 Nov. ZERO

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