Hexanal/-ol Massively Increases Dopamine Release - Good Or Bad Though?

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
There are a bunch of interesting studies on "Green odor" effects on dopamine content and release in the striatum of living rats - and also striatum sclices in the test-tube. The papers are mostly from 2008-2011 and from the same japanese authors barring one paper.

Green odor consists of 4 alcohols and fou aldehydes:
n-hexanol, (E)-2-hexenol, (Z)-3-hexenol, and (E)-3-hexenol, and four aldehydes, n-hexanal, (E)-2-hexenal, (Z)-3-hexenal, and (E)-3-hexenal ---- (z)=cis, (E)=trans

At least cis-3-hexenol (leaf alcohol) is a widely available and cheap substance used mostly in perfumery - and might be effective in inducing dopamine release spikes maybe by just inhaling a certain conentration-aerosol.
It is though not quite clear to me if this effect wold be beneficial in the long run even if used occasionally becuase I don't fully understand the mechanisms involved. The papers eludicate them in depth so maybe some of you can help interprete the effects and mechanism.



Effects of direct exposure of green odour components on dopamine release from rat brain striatal slices and PC12 cells. (2008)

Kako H1, Fukumoto S, Kobayashi Y, Yokogoshi H.
https://www.ncbi.nlm.nih.gov/pubmed/18355650#
Abstract

The effects of odour components on dopamine release from rat brain striatal slices and rat pheochromocytoma (PC12) cells were examined. The striatal slices were directly stimulated with 0.5% odour-including Krebs buffer using a superfusion method. In this experiment, (Z)-3-hexenol, (E)-2-hexenal, n-hexanal, 1,8-cineole or Eucalyptus globulus essential oil was used as an odour component. The concentrations of monoamines released in perfusate were measured by HPLC-ECD. Dopamine release from brain slices was significantly enhanced by perfusion of each odour-including solution. In particular, administration of n-hexanal caused a 9-fold increase in dopamine release. The dopamine release by n-hexanal increased linearly with the concentration of n-hexanal up to 0.5% and was maximal at 0.5%. Since PC12 cells have the ability to release dopamine, the effects of four green odour compounds, (Z)-3-hexenol, (E)-2-hexenal, n-hexanal and n-hexanol, on dopamine release were examined. These odour compounds dose dependently increased dopamine release from PC12 cells, and different patterns of dopamine release were observed with aldehyde or alcohol. Odour compounds thus appear to increase dopamine release from dopamine-releasing cells, with differences between aldehydes and alcohols in pattern of release. Dopamine regulates brain functions such as reward, mood, and attention. Green odours may in turn regulate such brain functions through the stimulation of dopamine release.

So here both alcohols and aldehydes induce release of dopa in dose-dependent manner in both striatal sclices and PC-12 cells, with differences between aldehydes and alcohols.

This paper follows up, which describes some of the mechanisms involved:




Contribution of intracellular Ca2+ concentration and protein dephosphorylation to the induction of dopamine release from PC12 cells by the green odor compound hexanal.

n-Hexanal (hexanal), a straight-chain six-carbon aldehyde, is mainly present in plants. Hexanal strongly affects the release of dopamine from rat striatal slices and rat pheochromocytoma (PC12) cells. In this study, we attempted to clarify the mechanism underlying the regulation of dopamine release by hexanal by using PC12 cells, which have the ability to synthesize, store, and release dopamine. The stimulation of PC12 cells with hexanal enhanced dopamine release in a time- and dose-dependent manner. Dopamine release was partially inhibited by pretreatment of the cells with BAPTA-AM, a cell-permeable Ca2+ chelator. In addition, the intracellular Ca2+ concentration was found to slowly increase after hexanal stimulation. Furthermore, the Src tyrosine kinase inhibitor PP2 partially inhibited hexanal-induced dopamine release. However, the levels of phosphorylated proteins decreased after hexanal stimulation. Hexanal stimulated the release of only a small amount of dopamine from reserpine-treated PC12 cells, in which the vesicular dopamine was depleted. These findings suggest that both an increase in the intracellular Ca2+ concentration and the dephosphorylation of phosphorylated proteins might be required for hexanal-stimulated release of dopamine, and that the dopamine released because of hexanal stimulation mainly comes from the dopamine vesicles. This study showed the cellular events that occurred in PC12 cells after stimulation of hexanal. Furthermore, it is important to examine the relationship between the cellular functions and the physiological effects of hexanal on dopamine release.


So intracellular Ca+ increase is involved in dopamine-release form PC12 cells. The red part then describes some moe celluar happenings but I don't know if those are "benign".
Would dephosphorylation of phosphorylated proteins lead to a sort of Dopamine-exhausting/kind of burn out. It seems this is an alternation of the cell with potentially longer lasting effects.

.


 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
It goes on with this:

Effects of n-hexanal on dopamine release in the striatum of living rats.
Kako H1, Kobayashi Y, Yokogoshi H.
Abstract
Green odor is present in many green leaves, vegetables, and fruits and is composed of four 6-carbon straight-chain alcohols, n-hexanol, (E)-2-hexenol, (Z)-3-hexenol, and (E)-3-hexenol, and four aldehydes, n-hexanal, (E)-2-hexenal, (Z)-3-hexenal, and (E)-3-hexenal. It has been reported that certain green odor compounds enhance dopamine release from rat brain striatal slices and rat pheochromocytoma cells (PC12 cells). It is well known that intracellular Ca(2+) levels regulate dopamine release. The amount of dopamine released by n-hexanal-treated PC12 cells decreased in cells pretreated with a membrane-permeable Ca(2+) chelator. In this study, the effect of n-hexanal on dopamine release in the brain striatum of living rats was studied using an in vivo brain microdialysis system. Local stimulation with n-hexanal diluted in Ringer's solution to 0.01%, 0.05%, or 0.1% enhanced dopamine release in a concentration-dependent manner. The amount of dopamine released with 0.01% n-hexanal administration significantly declined when either extracellular or intracellular Ca(2+) levels decreased. Furthermore, the extracellular dopamine concentration increased with perfusion of nomifensine, an inhibitor of dopamine uptake into cells. When nomifensine was co-perfused with n-hexanal into the striatum, extracellular dopamine release increased further. Accordingly, the concentration of dopamine metabolite and the ratio of dopamine metabolite to dopamine decreased after treatment with n-hexanal. These responses were similar to those seen with KCl stimulation. These data suggest that n-hexanal stimulates dopamine release but does not inhibit dopamine uptake in the brain striatum of living rats, and that dopamine release associated with n-hexanal is regulated by both extracellular and intracellular Ca(2+) levels.


I'm at a loss as to what this would mean to the cells and how it would affect the individual. A sustainable dopamine-spike or more on the excitatory side ?



The most recent one (2012) researches a few other carbo-chain aldehydes and their effects, hexanal still stands out, but there is a difference in effects on PC12-cells and striatal sclices.

Dopamine release from rat pheochromocytoma (PC12) cells and rat brain striata induced by a series of straight carbon chain aldehydes with variations in carbon chain length and functional groups.
Kako H1, Kobayashi Y, Yokogoshi H.

Abstract

Green odor compounds, a group of 6-carbon (C6) aldehydes and alcohols, are able to enhance dopamine release from pheochromocytoma (PC12) cells, rat brain striatal slices, and brain striata in living rats. In this study, we examined the effects of aldehydes and alcohols with varying carbon chain lengths (2-9 carbons) and functional groups on dopamine release in PC12 cells, brain slices, and living rat brain. In PC12 cells, n-aldehydes and n-alcohols promoted dopamine release, and this effect was stronger as the carbon chain length increased. In rat brain slices, however, the maximum dopamine release was detected when stimulated by n-hexanal, while n-nonanal promoted the lowest level of release. In addition, C6 compounds with a hydroxyl, aldehyde, or carboxyl group enhanced the dopamine release from PC12 cells and striatal slices. In the microdialysis study, n-hexanal and n-hexanol enhanced dopamine release, while n-nonanal promoted lower activity than n-hexanol. The relationship of the concentration of the odor-related compounds and the amount of dopamine released differed between PC12 cells and brain slices. Dopamine release in the living rat brains was similar to that in brain slices. These data suggested that the length of the carbon chain correlated with the strength of dopamine release, and the functional groups further modified it. The distinction between PC12 cells and rat striata might be due to the differences in the cell structure or the target molecules within the cells.



 
OP
L

LeeLemonoil

Member
Joined
Sep 24, 2016
Messages
4,265
Haidut advised me that he thinks aldehydes are unsafe in high doses.
They are unbearable anyway if dosed to high in a perfume, but hexenol seems interesting still
 

Similar threads

Back
Top Bottom