Posted by bulldog2 on February 6, 2010, at 18:34:38 [reposted on February 22, 2010, at 1:21:00 | original URL]
In reply to Re: Did you actually read the studies you posted?? » bulldog2, posted by linkadge on February 6, 2010, at 17:22:20
> A quote from THE VERY FIRST STUDY YOU POSTED:
>
> "In laboratory tests with mice, researchers found prolonged exposure to dopamine through this pathway inactivated a regulatory protein in the brain known as Akt and caused the mice to behave like they were depressed in response to stress."
>
> This is my point. I'm not even going to read the others cause I'm assuming you havn't either.
>
> LinkadgeOf course I read all the studies. It is not valid to cherry pick when the study actually backs up the dopamine theory.
The reality is I use what works for me and that is what is my study. We all have to figure out what works for us as individuals.
Many of us are dopamine responders and that is a fact for us even if you believe it is not true.
You always complain how horrible the current drugs are yet you deny that dopamine may be a player in depression.
You were also very rude to Floatingbridge. That is a reality for her and her doctor's conclusion. You owe her an apoligy for your response.
I'm not saying that dopamine is all that has to be tweeked. I know you despise ssirs. We are saying that drugs that lower dopamine or do not raise it may be missing a piece of the puzzle. Obviously since dopamine is a neurotransmitter in our brains it must have a function. If we tinker with se and ne why is dopamine off limits. ? Even sjw by some accounts raises dopamine.
Read And Enjoy from "The Good Drug Guide"
THE DOPAMINE CONNECTION
What's missing, crucially, is the therapeutic enrichment of hedonic tone via a combination of mu opioid pathway enhancement and prolonged stimulation of meso(cortico-)limbic dopamine function.This is really much more fun than it sounds. Yet the socially responsible use of reward pathway enhancements/remedial therapies is a technical, bioethical and medico-legal minefield. Complications aside, the currently available experimental evidence has persuaded many - but not all - investigators that the mesolimbic dopamine system serves as the final common pathway for pleasure in the brain. Enhanced responsiveness of post-synaptic dopamine D2/D3 receptors is vital to long-term emotional well-being. Insofar as they work, all "serotonergic" and "noradrenergic" mood-brighteners eventually act on the mesolimbic dopamine pathway, albeit in differing degrees and with varying delay. Even SSRIs depend on sensitization of the mesolimbic dopamine D2 receptors for their (modest) mood-lifting effect. New anti-Parkinsonian agents, notably the neuroprotective dopamine D3 receptor subtype selective pramipexole (Mirapex), ropinirole (Requip), and cabergoline (Dostinex) owe their potential role as fast-acting pro-sexual antidepressants to their dopaminergic action. Likewise, the possible mood-brightening effect of low doses of the dopamine receptor antagonist amisulpride (Solian), more commonly considered an antipsychotic agent, is explicable because amisulpride preferentially blocks the presynaptic dopamine D2/D3 autoreceptors; dopaminergic transmission is thereby enhanced.
The full story is inevitably complex. Dopamine agonists and reuptake inhibitors are often inadequate long-term mood-brighteners by themselves. The mesolimbic dopamine system mediates reward-signalling, incentive salience and a sense of urgency and significance, not the essence of pure bliss. Dopamine isn't itself the magic pleasure-chemical, though its functional role in conjunction with glutamate and mu opioid agonists in regulating medium spiny neurons of the rostromedial shell of the nucleus accumbens is critical. Researchers into affective disorders can prematurely become over-attached to one particular neurotransmitter system, its receptor sub-types and their signal-transduction cascades. Traditionally, serotonin and noradrenaline have attracted the fiercest rival partisans in antidepressant research. "Dopaminergic" (and opioid) agents, by contrast, are suspect. They are politically incorrect since they are potentially "abusable". Moreover it can be argued that the research and development of safe and sustainable Ecstasy-like empathogens and sociabilisers is at least as morally urgent as the license of safe and sustainable euphoriants. At any rate, enhanced mesolimbic dopamine release, exclusively or otherwise, enriches the intensity of experience; increases pleasure and libido, and potentially boosts cognitive performance. Even better, whereas some dopaminergics are potentially toxic, some dopamine-enhancing agents may have neuroprotective properties as well.
So what are the other contemporary options for chemical life-enhancement?
METHYLPHENIDATE (RITALIN); MINAPRINE (CANTOR); NOMIFENSINE (MERITAL)
A SSRI can be combined ("augmented" sounds more soothing to the official medical ear) with a dopaminergic such as methylphenidate. As Ritalin, methylphenidate is prolifically dispensed to American schoolchildren for different purposes altogether. It is sometimes abused as an instrument of social control. In spite of its structural relationship to amphetamine, methylphenidate resembles in many ways a more benign version of cocaine, yet with a much longer half-life. Methylphenidate blocks the reuptake of, but doesn't significantly release, the catecholamines noradrenaline and dopamine. If it is taken in sustained-release form or combined with an SSRI, all of which have anti-obsessive-compulsive properties too, then the likelihood of dose-escalation is minimised. In Europe and North America, students sometimes take Ritalin to gain a competitive edge in exams. However, its long-term effect on the developing brain is poorly understood.Chewing coca leaves with a dash of powdered lime is a nutritious and energising way to sustain healthy mood. Unfortunately, it's illicit and not very good for one's teeth.
A more cautious but still interesting option might be minaprine (Cantor). Minaprine blocks the reuptake of both dopamine and serotonin. It is also in some degree cholinomimetic. Thus it may exhibit both mood-brightening and nootropic properties. Much more research is needed. Unfortunately, minaprine is now obtainable only as a "research chemical".
Merital (nomifensine) showed great promise as a pleasantly stimulating dopaminergic that also potently inhibits the reuptake of noradrenaline and - to a much lesser extent - serotonin. It was marketed by its manufacturers Hoechst with the slogan "vive la difference!" Merital was withdrawn from licensed use after the discovery of its rare side-effect of precipitating a serious blood-disorder. For retarded melancholics, however, it was typically a very effective and well-tolerated mood-brightener with minimal side-effects. The risk/reward ratio of its carefully-monitored use may have been misjudged. Nomifensine is now obtainable only as a research chemical too.
And than there is amineptine that the US effectively had banned.
Dopamine is no diiferent than any of the other ads. For some depressed people raising serotonin may not be correct and the same may be true for norepinephrine.
It would seem to the most casual of observers that dopamine has to become part of the puzzle of creating a better ad. Why is ritalin part of your cocktail or at least was. It blocks reuptake of both ne and da.
I want more from my drug than being lifted out of depression and being a zombie than cannot feel pleaure because my med has depressed dopamine.
I don't understand how you can challenge people whose doctors with the patient symtoms present a picture of dopamine defeciency. Their clinical symtoms present that diagnosis. Your argument is studies that show how raising dopamine causes problems. Nobody is challening the fact that if dopamine is to high it can create problems.
The drug exctasy causes a massive release of serotonin. That causes people to feel touchy and feely and very sociable. Of course after the trip is over there can be massive depression. So you single out dopamine.
I can't really argue this with you anymore. Those of us who are dopamine responders understand the truth. For some of us this is our reality. Our minds are complex and we need a precise interactions of neurotransmitters. If one is titrated incorrectly the result will be bad.
Now if blocking dopamine for certain mental illness produces a good result does it not make sense that some may need a boost?
poster:bulldog2
thread:937616
URL: http://www.dr-bob.org/babble/neuro/20091104/msgs/937632.html