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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 14 of 14. This is the beginning of the thread.
Posted by Jamal Spelling on February 23, 2008, at 16:00:13
Dopaminergic and Glutamatergic Regulation of Effort- and Delay-Based Decision Making, Floresco SB, Tse MT, and Ghods-Sharifi S, Neuropsychopharmacology, September 2007.
Abstract:
Cost/benefit decisions regarding the relative effort or delay costs associated with a particular response are mediated by distributed dopaminergic and glutamatergic neural circuits. The present study assessed the contribution of dopamine and NMDA glutamate receptors in these different forms of decision making using novel effort- and delay-discounting procedures. In the effort-discounting task, rats could either emit a single response on a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a high-reward (HR) lever to obtain four pellets. In the delay-discounting task, one press of the HR lever delivered four pellets after a delay (0.5-8 s). A third task (effort-discounting with equivalent delays) was similar to the effort-discounting procedure, except that the relative delay to reward delivery was equalized across response options. The dopamine receptor antagonist flupenthixol reduced choice of the HR lever under all three testing conditions, indicating that dopamine antagonism alters effort-based decision making independent of any contribution of delay. Amphetamine exerted dose-dependent, biphasic effects; a higher dose (0.5 mg/kg) increased effort discounting, whereas a lower dose (0.25 mg/kg) reduced delay discounting. The noncompetitive NMDA antagonist ketamine (5 mg/kg) increased effort and delay discounting, but did not affect choice on the effort with equivalent delays task, indicating a reduced tolerance for delayed rewards. These findings highlight the utility of these procedures in pharmacologically dissociating the neurochemical mechanisms underlying these different, yet interrelated forms of decision making. Furthermore, they suggest that dopamine and NMDA receptors make dissociable contributions to these different types of cost-benefit analyses.------------------------------------
My question is: in the context of what they say about flupenthixol above, what do they mean by "dopamine antagonism alters effort-based decision making independent of any contribution of delay"?
Posted by Phillipa on February 23, 2008, at 17:16:34
In reply to Dopamine receptor antagonists, posted by Jamal Spelling on February 23, 2008, at 16:00:13
I was told that ketamine was in the general anesthesia I got. Man I'm stupid when it comes to this stuff. Phillipa
Posted by Phillipa on February 23, 2008, at 18:29:17
In reply to Re: Dopamine receptor antagonists » Jamal Spelling, posted by Phillipa on February 23, 2008, at 17:16:34
Wow didn't know it was a potent med or drug. Here's a link I found. Are you looking at depression? Wiki uses that term a lot TDR. Love Phillipa
Ketamine
Street terms for Ketamine: jet, super acid, Special "K", green, K, cat Valium1
What does Ketamine look like?
Ketamine comes in a clear liquid and a white or off-white powder form.
How is Ketamine used?Ketamine is a tranquilizer most commonly used on animals.
The liquid form can be injected, consumed in drinks, or added to smokable materials.
The powder form can be used for injection when dissolved.2
In certain areas, Ketamine is being injected intramuscularly.3
Who uses Ketamine?Ketamine, along with the other "club drugs," has become popular among teens and young adults at dance clubs and "raves."
How does Ketamine get into the United States?Marketed as a dissociative general anesthetic for human and veterinary use, the only known source of Ketamine is via diversion of pharmaceutical products.
Recent press reports indicate that a significant number of veterinary clinics are being robbed specifically for their Ketamine stock.
DEA reporting indicates that a major source of Ketamine in the United States is product diverted from pharmacies in Mexico.4
How much does Ketamine cost?Prices average $20 to $25 per dosage unit.5
What are some consequences of Ketamine use?Higher doses produce an effect referred to as "K-Hole," an "out of body," or "near-death" experience.6
Use of the drug can cause delirium, amnesia, depression, and long-term memory and cognitive difficulties. Due to its dissociative effect, it is reportedly used as a date-rape drug.7
Posted by yxibow on February 24, 2008, at 7:36:09
In reply to Re: Dopamine receptor antagonists » Jamal Spelling, posted by Phillipa on February 23, 2008, at 17:16:34
> I was told that ketamine was in the general anesthesia I got. Man I'm stupid when it comes to this stuff. Phillipa
Its normally used as a special pediatric anaesthetic these days. Its a dissociative and yes it is a powerful substance and a rather dangerous street agent which lands people in hospital (I've known this to happen to someone personally.) Dextromethorphan, cough syrup, is a modest dissociative in high quantities when people abuse Robitussin which is why it is now 18+ in the US.
It is also a horse/veterinary tranquilizer and operative more commonly.
Posted by yxibow on February 24, 2008, at 7:48:01
In reply to Dopamine receptor antagonists, posted by Jamal Spelling on February 23, 2008, at 16:00:13
> Dopaminergic and Glutamatergic Regulation of Effort- and Delay-Based Decision Making, Floresco SB, Tse MT, and Ghods-Sharifi S, Neuropsychopharmacology, September 2007.
>
> Abstract:
> Cost/benefit decisions regarding the relative effort or delay costs associated with a particular response are mediated by distributed dopaminergic and glutamatergic neural circuits. The present study assessed the contribution of dopamine and NMDA glutamate receptors in these different forms of decision making using novel effort- and delay-discounting procedures. In the effort-discounting task, rats could either emit a single response on a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a high-reward (HR) lever to obtain four pellets. In the delay-discounting task, one press of the HR lever delivered four pellets after a delay (0.5-8 s). A third task (effort-discounting with equivalent delays) was similar to the effort-discounting procedure, except that the relative delay to reward delivery was equalized across response options. The dopamine receptor antagonist flupenthixol reduced choice of the HR lever under all three testing conditions, indicating that dopamine antagonism alters effort-based decision making independent of any contribution of delay. Amphetamine exerted dose-dependent, biphasic effects; a higher dose (0.5 mg/kg) increased effort discounting, whereas a lower dose (0.25 mg/kg) reduced delay discounting. The noncompetitive NMDA antagonist ketamine (5 mg/kg) increased effort and delay discounting, but did not affect choice on the effort with equivalent delays task, indicating a reduced tolerance for delayed rewards. These findings highlight the utility of these procedures in pharmacologically dissociating the neurochemical mechanisms underlying these different, yet interrelated forms of decision making. Furthermore, they suggest that dopamine and NMDA receptors make dissociable contributions to these different types of cost-benefit analyses.
>
> ------------------------------------
>
> My question is: in the context of what they say about flupenthixol above, what do they mean by "dopamine antagonism alters effort-based decision making independent of any contribution of delay"?Basically from what I can discern this is a rat study that shows that the dopamine blockade in APs reduces confusion and decision making, at least in an animal model.
And in fact, though I am not taking it for its true label, Seroquel does reduce confusion and organizes my thoughts in as best a manner as there is an agent out there that the benefits still outweigh the risks at the moment.
But I'm reading into it myself.
Flupenthixol is a fairly powerful typical agent but occupies D2 slightly less than Haldol. It is used in noncompliant (aggressive, which is usually not the most common display of schizophrenia from what I know of) situations as well, although a number of depot agents including atypicals are available.
Posted by Jamal Spelling on February 24, 2008, at 9:09:17
In reply to Re: Dopamine receptor antagonists » Jamal Spelling, posted by yxibow on February 24, 2008, at 7:48:01
Thank you for your informative post, Jay.
There is also an oral formulation of flupentixol, known as Fluanxol, which is used in doses <= 3 mg/day to treat depression and anxiety. Years ago I used it at 0.5 mg/day for a period of 2.5 years with fantastic results. I am considering going back on it. It was the one psychotropic which I can truly say "worked" for me. I'm just scared I'll get TD or diabetes or something. I've searched PB archives and I've found posts by "dingbat" and "Ed_UK" suggesting the TD risk from low dose flupentixol is less than the diabetes risk from low dose Zyprexa. My doctor said she doesn't think I need to worry about TD at such a low dose, but I'm still scared.
Do you think TD is a serious risk factor at a dose of 0.5 mg/day flupentixol? The dose they use for psychosis is I think of the order 10 mg/day, but I stand to be corrected.
My problem is mainly that lately I get episodes which last about an hour at a time, where I become extremely depressed, pessimistic, anxious and full of rage, all at the same time. My thinking also becomes irrational in that I'll believe that certain people *hate* me etc. During these episodes I feel disconnected from reality and I also engage in acts of self-injury. Outside these episodes I'm fine. I think an AP would work well.
Flupentixol is unusual in that, at low doses at least, it has activating properties and is considered pro-motivational. That was certainly my experience with it back when I used to take it. The authors below argue that flupentixol should be classified as a partial atypical.
---------------------------------
Kühn K. U., Meyer K., and Maier W.,
Flupenthixol--a partial atypical neuroleptic?,
Fortschritte der Neurologie-Psychiatrie 68 Suppl 1:S38-41,
2000.Abstract:
There is no really clear-cut definition for "atypical" neuroleptics. The most convincing definition is draft by characterization of the receptor-binding profile. Most important are: the combined antagonism of D2 and 5-HT2 receptors, the preferential binding to D4 and D3 receptors and a balanced relation of D2 to D1 antagonism. Flupentixol fits into this description as well as some modern neuroleptics widely considered as "atypical" neuroleptics. Clinical criteria--like the absence of EPMS and the improvement of negative symptoms--offer no clear-cut distinction between "typical" and "atypical" neuroleptics, too, because some modern "atypical" neuroleptics lead--dose-dependent--to EPMS, and there is no proven efficacy for some atypical neuroleptics in the treatment of negative symptoms. So, neuroleptics are labelled "atypical" if there is a favourable relation between antipsychotic activity and the degree of EPMS, and if there is at least some efficacy in the treatment of negative symptoms. In this regard, Flupentixol has to be labelled at least a "partial atypical neuroleptic".---------------------------------
Posted by Jamal Spelling on February 24, 2008, at 11:08:31
In reply to Re: Dopamine receptor antagonists » yxibow, posted by Jamal Spelling on February 24, 2008, at 9:09:17
This is not what I was hoping to see.
---------------------------
Eur Neuropsychopharmacol. 1997 Nov;7(4):261-6.Click here to read Links
Tolerability of low dose neuroleptics: a case control study of flupenthixol.
Fritze J, Spreda I.Klinik für Psychiatrie und Psychotherapie I, Zentrum der Psychiatrie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
There are no data available on the risk of extrapyramidal symptoms when using long-term flupenthixol in low dosage in patients suffering from anxiety and depressive disorders. In a case control study 106 patients essentially treated with the neuroleptic flupenthixol in a so-called low, non-antipsychotic dosage were compared to n=37 otherwise comparable patients who never had been treated with neuroleptics. The investigator was blind to the previous treatment conditions. Extrapyramidal symptoms were found although with a low prevalence and mild degree: 6.7% tardive dyskinesia, none in controls; pseudoparkinsonism 26%, 16% in controls. Extrapyramidal side-effects, especially tardive dyskinesia, have to be considered in the individual weighing of therapeutic benefits and risks even when prescribing flupenthixol in low dosages.
PMID: 9443657 [PubMed - indexed for MEDLINE]
---------------------------
Posted by Phillipa on February 24, 2008, at 13:20:32
In reply to Re: Dopamine receptor antagonists » Phillipa, posted by yxibow on February 24, 2008, at 7:36:09
Jay could you write to me as can't sit up? Thanks Phillipa
Posted by yxibow on February 25, 2008, at 1:06:36
In reply to Scary, posted by Jamal Spelling on February 24, 2008, at 11:08:31
> This is not what I was hoping to see.
>
> ---------------------------
>
> Eur Neuropsychopharmacol. 1997 Nov;7(4):261-6.Click here to read Links
> Tolerability of low dose neuroleptics: a case control study of flupenthixol.
> Fritze J, Spreda I.
>
> Klinik für Psychiatrie und Psychotherapie I, Zentrum der Psychiatrie, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
>
> There are no data available on the risk of extrapyramidal symptoms when using long-term flupenthixol in low dosage in patients suffering from anxiety and depressive disorders. In a case control study 106 patients essentially treated with the neuroleptic flupenthixol in a so-called low, non-antipsychotic dosage were compared to n=37 otherwise comparable patients who never had been treated with neuroleptics. The investigator was blind to the previous treatment conditions. Extrapyramidal symptoms were found although with a low prevalence and mild degree: 6.7% tardive dyskinesia, none in controls; pseudoparkinsonism 26%, 16% in controls. Extrapyramidal side-effects, especially tardive dyskinesia, have to be considered in the individual weighing of therapeutic benefits and risks even when prescribing flupenthixol in low dosages.
>
> PMID: 9443657 [PubMed - indexed for MEDLINE]
>
> ---------------------------If you scour pubmed for journals you'll come across small patient studies all the time. That doesn't mean it is what flupenthixol is, in your body.
The minimum effective dose of any AP is always good, and as I said in my previous posting, which you can search, the MED, minimum effective dose is always the best.
A very low dose of a typical AP probably carries a lower risk over a long time than a higher one.
But as I said, the accepted theory now is that it is about 5% per year per a maximum lifetime of about 25%. But statistics go only so far. They're very messy and are not completely linear. Genetics, brain differences, everything contributes.
For myself, I dont like taking any but even with a tic that I probably did get (and this is rare) from an atypical because I had high doses over long periods of time... the risk of things like Zyprexa and Seroquel are in the 0.1% range accepted today. Risperdal is higher, perhaps closer to the typicals in high doses and has had cases of TD, but not large cases yet.
It is true that typicals for the most part are just as effective as atypicals for schizophrenia and certain disorders, as in the CATIE study -- and for that reason NHS in the UK and other public health systems use them more. But at what price glory -- the risks are a bit higher, a lot higher at high doses and high potency, and mainly the side effects, called EPS, extrapyramidal symptoms like akathisia and pseudoparkinsonism (which go away with discontinuation basically) are less with atypicals for most people. Some people don't have much with typicals. So there's another statistical variation. I can't possibly stand Compazine (for vomiting), it made me run through the walls in an ER situation the akathisia was so high. But phenothiazines are potent typicals. On the other hand I get akathisia even with some of the stronger typicals like Geodon. Of course nothing like the prior experience.
Yes, people are scared to take the medication. I am scared to take the medication, but I guess I'm fatalistic about it at the moment -- for the short time now, I need it for my clarity. In the long run I dont know, do I risk Clozaril, or do I continue Seroquel, or what. And on top of this of course, its not all medication, there are psychological things to consider, a lot. And people really don't get enough psychological counseling in the US because the HMO system doesn't like paying for it long term. But thats my soapbox.Anyhow I hope that helped a bit about things.
-- Jay
Posted by yxibow on February 25, 2008, at 1:08:17
In reply to Re: Dopamine receptor antagonists » yxibow, posted by Phillipa on February 24, 2008, at 13:20:32
> Jay could you write to me as can't sit up? Thanks Phillipa
Sit up? I hope you din't break anything, or are you talking about the other issues of surgery. Anyhow, you can feel free to babblemail, I usually am able to get to it through the junk and all.
Posted by Jamal Spelling on February 25, 2008, at 14:45:06
In reply to Re: Dopamine receptor antagonists » Jamal Spelling, posted by yxibow on February 24, 2008, at 7:48:01
> Basically from what I can discern this is a rat study that shows that the dopamine blockade in APs reduces confusion and decision making, at least in an animal model.
By "reduces ... decision making", do you mean it reduces indecisiveness and procrastination?
Posted by yxibow on February 25, 2008, at 15:54:19
In reply to Re: Dopamine receptor antagonists » yxibow, posted by Jamal Spelling on February 25, 2008, at 14:45:06
> > Basically from what I can discern this is a rat study that shows that the dopamine blockade in APs reduces confusion and decision making, at least in an animal model.
>
> By "reduces ... decision making", do you mean it reduces indecisiveness and procrastination?What I am deducing from reading the article is yes, indecisiveness and confusion and other things. Schizophreniform disorders have negative and positive symptoms, as well as cognitive symptoms (not related to the dictionary terms of those words exactly).
"People diagnosed with schizophrenia usually experience a combination of positive (i.e. hallucinations, delusions, racing thoughts), negative (i.e. apathy, lack of emotion, poor or nonexistant social functioning), and cognitive (disorganized thoughts, difficulty concentrating and/or following instructions, difficulty completing tasks, memory problems)."
[http://www.schizophrenia.com/diag.php]
There are a lot more detailed descriptions but what I think was being tested here was cognitive and possibly negative symptoms.I'm not the expert on schizophrenia, though, but from what I do know, almost entirely all the people who are schizophreniform are not violent like the media portrays. Its really shameful.
And then there's a certain belief system(s) which I wont post here for sake of arguments, PBCs, and the like, that shuns medication, which has caused tragedies with the few people who do have positive symptoms.-- Jay
Posted by Jamal Spelling on February 25, 2008, at 16:15:16
In reply to Re: Dopamine receptor antagonists » Jamal Spelling, posted by yxibow on February 25, 2008, at 15:54:19
Posted by Jamal Spelling on February 26, 2008, at 15:07:12
In reply to Re: Dopamine receptor antagonists » Jamal Spelling, posted by yxibow on February 24, 2008, at 7:48:01
> And in fact, though I am not taking it for its true label, Seroquel does reduce confusion and organizes my thoughts in as best a manner as there is an agent out there that the benefits still outweigh the risks at the moment.
I saw my pdoc today and mentioned to her I might be interested in resuming Fluanxol. She said she's OK with that, although she'd prefer I rather try Seroquel if I'm going to be taking an AP.
But first she wants me to try Cymbalta on its own for a month. She thinks "it's the one". Before I start the Cymbalta though, she wants me to go for an EEG to rule out neurological issues. So I'll probably only start Cymbalta in about 3 weeks' time, assuming the EEG is fine, because my EEG is only scheduled for 2 weeks from now.
These delays are so frustrating.
This is the end of the thread.
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