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No good/bad guys, just a bunch of crazy receptors

Posted by Brainbeard on May 29, 2010, at 15:04:12

In reply to Re: Prozac, 5HT2C And The Trojan Horse In Lisuride, posted by CrAzYmEd on May 29, 2010, at 8:44:34

> "Anyhow, 5HT2A-agonism inhibits the benefits of both 5HT1A- and 5HT2C-agonism. "
>
> DO you have a source that 5HT2A agonism inhibits the beneficial effect of 5HT1A agonism?

>id definatly would like to see some studies that it inhibits the positive effects of 5HT1A.

It's given in the study mentioned above (Gerard J Marek, Linda L Carpenter, Christopher J McDougle and Lawrence H Price: 'Synergistic Action of 5-HT2A Antagonists and Selective Serotonin Reuptake Inhibitors in Neuropsychiatric Disorders', in: Neuropsychopharmacology (2003) 28, 402412, link: http://www.nature.com/npp/journal/v28/n2/full/1300057a.html). Quote:

'INTERACTIONS BETWEEN 5-HT2A AND 5-HT1A RECEPTORS

At a cellular level, activation of 5-HT2A and 5-HT1A receptors exerts depolarizing and hyperpolarizing effects, respectively, on cortical pyramidal cells (Araneda and Andrade, 1991; Tanaka and North, 1993; Ashby et al, 1994; Aghajanian and Marek, 1997). These interactions have been observed both under in vitro conditions and during in vivo recordings from the rodent medial prefrontal cortex. Similar interactions have also been observed at a behavioral level. For example, stimulation of 5-HT1A receptors suppresses head shakes in rats induced by hallucinogenic drugs, which activate 5-HT2A receptors (Arnt and Hyttel, 1989; Schreiber et al, 1995). Previous studies have demonstrated that systemic administration of 5-HT1A agonists can block head shakes induced by direct infusion of the hallucinogen 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) into the medial prefrontal cortex (Granhoff et al, 1992; Willins and Meltzer, 1997).

Evidence for opposing effects of activation of 5-HT2A and 5-HT1A receptors has also been obtained from a behavioral screen for antidepressant drugs, rats performing on a differential reinforcement of low rate 72-s (DRL 72-s) schedule (Marek et al, 1989a,1989b; Marek and Seiden, 1994; Jolly et al, 1999). This behavioral screen measures a cardinal feature of prefrontal cortical 'executive function,' that is, withholding inappropriate responses (Fuster, 1997). At an operational level, water-deprived animals in this paradigm must wait at least 72 s following the previous response in order to receive a reinforcer (water) for making a response. The efficacy of 5-HT antagonists in exerting an antidepressant-like response on this screen (increased reinforcement rate, decreased response rate, and a cohesive rightward shift in the inter-response time (IRT) histogram) is related to the selectivity of the antagonists for 5-HT2A relative to 5-HT1A receptors (Marek et al, 1989a; Marek and Seiden, 1994).'

There are no 'good guys' and 'bad guys'; there are several complex and intertwined mechanisms striving for a delicate balance.


Current meds: 10mg melitracene + 0.5mg flupentixol; sertraline 100mg; amitriptyline 25mg; gabapentin (Neurontin) 300mg; melatonin 0.3mg. PRN: diazepam (Valium) 2.5-5mg.


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poster:Brainbeard thread:948688
URL: http://www.dr-bob.org/babble/neuro/20100223/msgs/949416.html