Opioid receptor knockout mice
by
Sora I Department of Psychopharmacology,
Tokyo Institute of Psychiatry, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi 1999 Dec; 19(5):239-49

ABSTRACT
Mu, delta, kappa opioid receptors are target molecules for analgesia, reward and many physiological functions of opiates. Opioid receptor knockout mice generated by gene-targeting technology which can introduce mutation into specified locus provide invaluable animal models to elucidate the in vivo function of opiates and develop new therapeutic drugs. The disruptions of mu receptor expression decreases the nociceptive threshold to thermal stimuli and increases the threshold to visceral chemical stimuli paradoxically. Analgesia, reward, respiratory depression, constipation, immunosuppression and physical dependence induced by morphine are absent in mice lacking the mu receptor. These data show that the mu receptor is a molecular target for most effects of morphine, both therapeutic and side effects. mu Receptor expression is required for most delta receptor-mediated and some kappa receptor analgesic effects. These results support substantial roles for mu receptor in the analgesic properties of delta, kappa receptors. Cocaine and ethanol reward require mu receptor systems' intactness. Mice lacking the mu receptor will be a useful tool to study complex interactions between endogenous opiate and dopamine systems.

Just think if someone is born with less Mu receptors than normal, or devolops less. that person will have less pleasure and more depression in their life, for their whole life. also a person with more mu receptors than another person could have a much better life. you never know

I never felt normal in my life until i had an opioid. it lessened all the severe dysphoria depression, social phobia, panic, anxiety, lack of concentration, and other severe life long problems

I dunno, Tone. Maybe smack is a legitimate neurochemical therapy for some people. The problem is, smack usually becomes a real problem for most people and as such a powerful stigma has developed around it.

i hate smack. tramadol is the best one. hydrocodone and oxycodone are also much better. morphine and smack are the worst one, they are teh least stimulating and most sedating and feel board and blah compared to the others.

I'm abusing the word 'smack' to refer to opioids, although clearly the word ordinarily refers to heroin which is a bit over the top compared to the rest. It's my experience that 'addiction' is only clear in hindsight, thus I cannot trust that a person can really know whether or not the road they are going down will end as 'addiction' but I can predict the odds of it happening based on available evidence. Such odds seem to be stacked against the user in the case of opioids

just think, as the new painkiller pills with DAMGO or Low Dose Naltrexone mixed in with them are perfected at just the right dose, it would minimize the devolopment of tolerance because it keeps receptors more sensitive -- you know what that also means? it means when the person quits the pills they dont nearly go through as much withdrawal as with normal pain pills. this is because 1) the additive has kept the receptors more sensitive so they dont have to upregulate back to normal as much and 2) they never go beyond a standard dose because theres no need to keep going up as tolerance is not a probablem anymore, therefore they are withdrawling from a low standard dose and not some high dose they worked up to.

so that means addiction is less of an issue with the new pills that hinder tolerance

is it possible to only enhance the sensitivity of receptors without introducing non-native opioids?

i do not understand the question....

can one ingest 'opioid recepter sensitizers' and gain satisfactory results without also ingesting opioids?

A very interesting question, Dan.

Tone, is you physician, who is helping you with these combinations, going to publish his results so that others can similarly be helped? I think this approach has some potential for the treatment of heroin addiction too.

hi rick, stuff on ultra low dose naltrexone with opioids to minimize tolerance have allready been long published. infact there is already a new drug called OxyTrex that combines naltrexone with oxycodone thats in phase III clinical trials now. just search something like: tolerance Naltrexone Opioid in a search engine or pubmed. heres a few:

COmpany Producing Oxytrex
http://www.paintrials.com/oxytrex.html

News Story about OxyTrex
http://www.opioids.com/tolerance/oxytrex.html

Queen's Researchers Discover Paradox Of Pain Control; Morphine Effectiveness Restored To Between 80 And 90% Of Original Amount
http://opioids.com/tolerance/paincontrol.html