5 replies to this topic

[BioInfinite]

The delta-opioid receptor agonist (+)BW373U86 regulates BDNF mRNA expression in rats.

Torregrossa MM¹, Isgor C, Folk JE, Rice KC, Watson SJ, Woods JH.

Author information

 

Abstract

delta-Opioid receptor agonists have antidepressant-like effects in behavioral models of depression. Chronic administration of classical antidepressants upregulates mRNA expression of brain-derived neurotrophic factor (BDNF) and its high-affinity tyrosine kinase receptor, TrkB in the frontal cortex and hippocampus of rats. Increases in BDNF and TrkB levels are thought to be important for the therapeutic effects of these drugs. Therefore, we examined the ability of the delta-opioid receptor agonist (+)BW373U86 to regulate BDNF and TrkB mRNA expression in frontal cortex, hippocampus, as well as, basolateral amygdala, endopiriform nucleus, and primary olfactory cortex. At 3 h after a single administration of (+)BW373U86 animals were killed and BDNF and TrkB mRNA levels were examined by in situ hybridization. BDNF mRNA levels produced by (+)BW373U86 were compared to acute administration of the antidepressants desipramine and bupropion. A behaviorally antidepressant dose of 10 mg/kg (+)BW373U86 increased BDNF mRNA expression in all regions examined; a smaller dose of (+)BW373U86 (1 mg/kg) significantly increased BDNF mRNA expression only in frontal cortex. The delta-opioid receptor antagonist naltrindole blocked (+)BW373U86-mediated increases in BDNF mRNA expression. In addition, tolerance developed to increased BDNF mRNA expression with repeated injection, except in frontal cortex. Midazolam was administered to some animals to prevent the convulsions produced by (+)BW373U86, but midazolam did not block delta-opioid receptor-mediated increases in BDNF mRNA expression in frontal cortex, hippocampus, or amygdala. Unlike desipramine and bupropion, (+)BW373U86 upregulated BDNF mRNA expression acutely (within 3 h after a single administration). These data support the concept that delta-opioid receptor agonists may have antidepressant potential, and could be good targets for the development of faster-acting antidepressants.

 

http://www.ncbi.nlm....pubmed/14647482

 

 

Does anyone have any idea if delta agonism indirectly increases Serotonin or Dopamine? I'm very interested to know what upregulated BDNF would do to monoamine levels.

[eon]

I wonder what could these drugs be and if Kratom is another good natural source considering it is a mu-opioid receptor agonist.

Edited by eon, 27 February 2015 - 10:41 AM.

[Galaxyshock]

Interesting, delta-opioid receptor is indeed a potential target for painkilling and antidepressant properties. My hunch feeling is that delta-opioid receptor is more connected to serotonin and mu-opioid receptor to dopamine. We know MOR agonists tend to be addictive, whereas I haven't heard of DOR agonists being abused?

 

Anyways, what available DOR agonists are there? I guess Kratom alkaloids work on delta too, but that herb is not available in Finland. I suspect Bacopa could be DOR agonist, I remember reading a study years ago about it's opioid-system properties but can't seem to find it anymore. Bacopa has that opiate-ish feeling to it but it's not rewarding like mu-agonists are.

[Daniel Cooper]

Interesting, delta-opioid receptor is indeed a potential target for painkilling and antidepressant properties. My hunch feeling is that delta-opioid receptor is more connected to serotonin and mu-opioid receptor to dopamine. We know MOR agonists tend to be addictive, whereas I haven't heard of DOR agonists being abused?
 
Anyways, what available DOR agonists are there? I guess Kratom alkaloids work on delta too, but that herb is not available in Finland. I suspect Bacopa could be DOR agonist, I remember reading a study years ago about it's opioid-system properties but can't seem to find it anymore. Bacopa has that opiate-ish feeling to it but it's not rewarding like mu-agonists are.

 
List at the bottom of this Wikipedia article.
 
δ-opioid receptor

[Galaxyshock]

 
List at the bottom of this Wikipedia article.
 
δ-opioid receptor

 

Good list, unfortunately most of the compounds are rather "exotic" and hard to get.

 

Amoxapine is on the list, it's a tricyclic antidepressant that has rather fast onset of action - perhaps indeed through DOR agonism.

 

Found this study about Bacopa:

https://academicjour...ct/D4E439B33106

Naloxone blocks its antinociceptive effects so an opioid (most likely at the delta receptor) effect is involved.

It also seems to have tolerance- and harm-reducing effects to common opioids.

[Galaxyshock]

Agmatine might work for tolerance for those interested in trying delta-opioid receptor agonists:

 

Abstract
Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, agmatine enhances morphine analgesia in a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater effect is observed when morphine is given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to the potentiation of morphine analgesia, agmatine (10 mg/kg) has no effect on morphine's inhibition of gastrointestinal transit. delta-Opioid receptor-mediated analgesia also is potentiated by agmatine, but kappa1-receptor-mediated (U50,488H; trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetemide) and kappa3-opioid receptor-mediated (naloxone benzoylhydrazone) analgesia is not significantly enhanced by any dose of agmatine tested in this acute model. In chronic studies, agmatine at a low dose (0.1 mg/kg) which does not affect morphine analgesia acutely prevents tolerance following chronic morphine dosing for 10 days. A higher agmatine dose (10 mg/kg) has a similar effect. Agmatine also blocks tolerance to the delta-opioid receptor ligand [D-Pen2,D-Pen5]enkephalin given intrathecally, but not to the kappa3-opioid receptor agonist naloxone benzoylhydrazone. Despite its inactivity on kappa1-opioid analgesia in the acute model, agmatine prevents kappa1-opioid receptor-mediated tolerance. These studies demonstrate the dramatic interactions between agmatine and opioid analgesia and tolerance.

→ source (external link)