Posted by zeugma on June 12, 2006, at 18:12:19
In reply to Re: Klonopins relationship to serotonin » zeugma, posted by SLS on June 12, 2006, at 10:42:16
hey Scott.
>>>
I didn't realize how important the striatum was for cognition.>>A lot of the research that's been done of this nature has been conducted in Parkinson's disease patients, who suffer a progressive depletion of DA from the dorsal striatum, which connects with the dorsal PFC, to the ventral striatum, which connects to the ventral PFC- a.k.a. the orbitofrontal PFC, said to be problematic for bipolars, and excessive stimulation of which (through L-Dopa therapy) produces such problems of excessive DA activity as the well-known 'pathological gambling' syndrome. L-Dopa actually produces highly variable cognitive effects in patients, depending on how far into the striatum the disorder has progressed. In patients with excessive striatal activity, a drug such as sulpiride can actually have cognitive benefits.
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I guess I'm trying to distinguish between the site of primary dysfunction and those areas that are affected as secondary.
>>That is an entirely worthwhile goal. I wish I knew more about the circuitry, but since I don't, I'll quote a passage that seems like it might be fruitful. It's from Elkhonon Goldberg's book on the PFC, "The Executive Brain", and he gets very explicit about neurotransmitters and regions of the brain that he thinks important in various syndromes, though he presents it as the result of a highly speculative Russian tradition that is not part of Western common currency:
"According to them [scientists at the Bourdenko Institute of Neurosurgery in Moscow], L-Dopa...improves the functions we typically associate with the posterior aspect of left frontal lobe: motor sequencing, speech initiation, expressive language....By the same token L-Dopa seems to retard the functions commonly associated with the parietal lobes (spatial orientation and spatial construction). L-glutamic acid...improves... other functions associated with the frontal lobes. It imporves insight into one's condition (reduces symptoms of anosognia), improves the sense of humor [!], time estimation, and time sequencing. L-glutamic acid also improves the functions typically associated with the parietal lobes [assuming modafinil works on this structure, this is indeed true. Modafinil does indeed improve my comedic abilities {source of its AD effects IMO}, but the parietal lobe is also associated with the "dorsal" stream I referred to in my previous post. And how Russian, to mention sense of humor as a faculty worthy of notice by neurologists! I am of Russian descent]. L-tryptophan...improves the functions of the parietal lobe but retards the functions of the frontal lobes, particularly the functions of the left frontal lobe. Ameridin, an anticholinesterase not commonly known in the United States, seems to improve the functions of the parietal lobes, particulary the left parietal lobe. It improves comprehension of grammar..." (pp.195-196)
I find these Russian speculations fascinating to revisit after i have taken drugs that mimic the effect of some of these substances, and I find they are remarkably congruent with my own experience and what I know of the Western tradition of neuroscience. It also shows how delicate the balance is between neurotransmitters and structures, and this is something Trevor Robbins, who is my main source for information on DA and the fronto-striatal pathways, emphasizes: 'cognition enhancers' inevitably have 'cognitive side effects.'
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Have you ever played with melatonin to help adjust your circadian rhythm?
>>That is an interesting idea. melatonin seems to be similar in some ways to serotonergetic manipulations, in particular blockade of the 5-HT 2A/C receptors, and also to 5-HT 1A agonism:
Eur Neuropsychopharmacol. 2006 Mar 6; [Epub ahead of print]
Melatonin affects the immobility time of rats in the forced swim test: The role of serotonin neurotransmission.Micale V, Arezzi A, Rampello L, Drago F.
Department of Experimental and Clinical Pharmacology, University of Catania, Catania, Italy.
The efficacy of melatonin or its derivatives in depressive patients has been recently considered for clinical application. However, the evidence for its effect on experimental models of depression is not consolidated. Here, the effects of melatonin on the model of forced swim test (FST) paradigm were studied in male rats of the Wistar strain after acute intraperitoneal (i.p.) administration of 0.1, 0.5 or 1 mg/kg of the hormone. Melatonin at doses of 0.5 and 1 mg/kg, but not of 0.1 mg/kg, decreased the immobility of rats in the FST paradigm suggesting a possible antidepressant-like activity. The dose of 0.5 mg/kg appeared to be as potent as clomipramine 50 mg/kg in reducing the immobility time of rats in the FST paradigm. The effect of melatonin on immobility time of rats in the FST paradigm was abolished by the simultaneous injection of the non-selective melatonin antagonist, luzindole (0.25 mg/kg, subcutaneously). Similarly, administration of small quantities of serotonin (5-HT, 5 ng/1 mul) or of the 5-HT(2A)/5-HT(2C) receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (2 ng/1 mul) injected into the amygdale totally suppressed the reduction of immobility time in the FST paradigm induced by melatonin 0.5 mg/kg. These results may suggest that effects of melatonin on the behavioral reaction of rats in the FST paradigm are due to an interaction of the hormone with central 5-HT neurotransmission.
J Pineal Res. 2002 Aug;33(1):14-9.
Melatonin potentiates 5-HT(1A) receptor activation in rat hypothalamus and results in hypothermia.Lin MT, Chuang JI.
Department of Medical Research, Chi-Mei Medical Center, Yung-Kang City, Tainan Hsien, Taiwan. mtlin@ym.edu.tw
Effects of melatonin on both thermoregulatory responses and hypothalamic serotonin release were assessed in unanesthetized rats at three different ambient temperatures (Ta). Systemic administration of melatonin (30-120 mg/kg, i.p) caused a decrease in both colonic temperature and hypothalamic serotonin (5-HT) release in rats at both Ta 8 and 22 degrees C. The hypothermia was brought about by a decrease in metabolic rate at Ta 8 degrees C, whereas at Ta 22 degrees C the hypothermia was produced by both a decrease in metabolic rate and an increase in cutaneous temperature. However, in the heat (Ta 31 degrees C), neither thermoregulatory responses nor hypothalamic 5-HT release was affected by the same amount of administered melatonin. The melatonin-induced hypothermia and decreased 5-HT release in the hypothalamus were attenuated by selective depletion of brain 5-HT produced by intracerebroventricular injection of 5,7-dihydroxytryptamine. Furthermore, the melatonin-induced hypothermia was almost completely abolished by treatment with a 5-HT2A receptor agonist (DOI) or a 5-HT1A receptor antagonist [(-)-pindolol]. The data indicate that melatonin potentiates the 5-HT1A receptor activation in the hypothalamus and results in hypothermic effects which can be antagonized by the expected hyperthermic effect of DOI.
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The sleep docs I saw advocated Xyrem, however my pdoc is I think rightly reluctant to try that prematurely. My circadian rhythms have always been dysregulated. I will see if melatonin has interactions with any of the meds I'm taking.
I value your conversation and insights greatly.
-z
poster:zeugma
thread:654917
URL: http://www.dr-bob.org/babble/20060610/msgs/656083.html