polarbearsarecool
Bluelighter
- Joined
- Jun 17, 2010
- Messages
- 67
Cholecystokinin (CCK) is an abundant and widely distributed neuropeptide that plays a modulatory role in a variety of behaviours including noiception, anxiety, memory, hunger
CCK has two main subtype receptors CCKa(primarily GI tract, less CNS) and CCKb(primarily CNS, less GI)
CCK is coupled with dopamine in neurons In many areas where CCK is colocalized with DA, the concentration of CCK is more than an order of magnitude greater than the concentration of DA (Rotzinger, Vaccarino)
CCK is coreleased with DA at high frequency firing rates, allowing the possibility of modulating DA function, but only under conditions that lead to this high frequency firing. (Rotzinger, Vaccarino)
CCK is colocalized with DA in most VTA cell bodies and terminals containing both CCK and DA are present in the Nacc (Rotzinger, Vaccarino)
The release is apparently coupled in the reward pathway and with drugs of abuse CCK acts competitively with dopamine, it has even been shown that drugs of abuse increase concentrations of CCK, namely in chronic users
So drugs of abuse cause epigenetic changes regarding CCK transcription(higher levels CCK, more DA competition)?
However, Proglumide a CCKb/a (mainly b) ANTAGONIST, blocks CCK binding thus stopping CCK's competitive inhibition of DA and sensitization on the reward pathway.
My question is regarding proglumide and amphetamine/psychadelics, CCK appears to be one of the first and major steps/cycles in the reward pathway.
My guess? Usage of proglumide doesn't stop/slow just opiate tolerance, but psychadelic and amphetamine tolerance by blocking the epigenetic changes drugs of abuse induce on the reward pathway.
Has any usage of well below recreational opiate level dosage( 100-300mg) been done in amounts of 10-50mg for a week? Or the usage of proglumide ~20mins before a psychadelic/amphetamine? Will there be added opiate receptor fog from proglumide, or does it's complementary abilities not work well on its own? If cycled could proglumide work? obviously the body builds a tolerance to it but...
Why is there no information on studies being done or human reports of this nature or of the combination of proglumide/something besides opiates? I cannot find any atypical studies, some show that CCK attenuates amphetamine responses, but it's not enough..
I also feel as if proglumide will attenuate modafinil tolerance.
"Stress exposure is known to cross-sensitize with psychostimulant administration, and CCK-A antagonists also attenuate the exaggerated (sensitized) locomotor response to amphetamine in rats that have been chronically restrained. This finding further suggests that CCK may play a common modulatory role in both the response to chronic stress and the response to chronic psychostimulants. CCK-A receptors appear to be involved only in the expression of sensitized behaviour, however, and not in its development." (Rotzinger, Vaccarino)
(more in pdf attached)
FULL PDF:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC161741/
Polarbears
CCK has two main subtype receptors CCKa(primarily GI tract, less CNS) and CCKb(primarily CNS, less GI)
CCK is coupled with dopamine in neurons In many areas where CCK is colocalized with DA, the concentration of CCK is more than an order of magnitude greater than the concentration of DA (Rotzinger, Vaccarino)
CCK is coreleased with DA at high frequency firing rates, allowing the possibility of modulating DA function, but only under conditions that lead to this high frequency firing. (Rotzinger, Vaccarino)
CCK is colocalized with DA in most VTA cell bodies and terminals containing both CCK and DA are present in the Nacc (Rotzinger, Vaccarino)
The release is apparently coupled in the reward pathway and with drugs of abuse CCK acts competitively with dopamine, it has even been shown that drugs of abuse increase concentrations of CCK, namely in chronic users
So drugs of abuse cause epigenetic changes regarding CCK transcription(higher levels CCK, more DA competition)?
However, Proglumide a CCKb/a (mainly b) ANTAGONIST, blocks CCK binding thus stopping CCK's competitive inhibition of DA and sensitization on the reward pathway.
My question is regarding proglumide and amphetamine/psychadelics, CCK appears to be one of the first and major steps/cycles in the reward pathway.
My guess? Usage of proglumide doesn't stop/slow just opiate tolerance, but psychadelic and amphetamine tolerance by blocking the epigenetic changes drugs of abuse induce on the reward pathway.
Has any usage of well below recreational opiate level dosage( 100-300mg) been done in amounts of 10-50mg for a week? Or the usage of proglumide ~20mins before a psychadelic/amphetamine? Will there be added opiate receptor fog from proglumide, or does it's complementary abilities not work well on its own? If cycled could proglumide work? obviously the body builds a tolerance to it but...
Why is there no information on studies being done or human reports of this nature or of the combination of proglumide/something besides opiates? I cannot find any atypical studies, some show that CCK attenuates amphetamine responses, but it's not enough..
I also feel as if proglumide will attenuate modafinil tolerance.
"Stress exposure is known to cross-sensitize with psychostimulant administration, and CCK-A antagonists also attenuate the exaggerated (sensitized) locomotor response to amphetamine in rats that have been chronically restrained. This finding further suggests that CCK may play a common modulatory role in both the response to chronic stress and the response to chronic psychostimulants. CCK-A receptors appear to be involved only in the expression of sensitized behaviour, however, and not in its development." (Rotzinger, Vaccarino)
(more in pdf attached)
FULL PDF:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC161741/
Polarbears
