So it seems that the Sigma receptors have a role in hypothalamic neurogenesis. This I got from the following studies:
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J Psychopharmacol. 2013 Oct;27(10):930-9. doi: 10.1177/0269881113497614. Epub 2013 Jul 17.
Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism.
Abstract
The putative antidepressant captodiamine is a 5-HT2c receptor antagonist and agonist at sigma-1 and D3 dopamine receptors, exerts an anti-immobility action in the forced swim paradigm, and enhances dopamine turnover in the frontal cortex. Captodiamine has also been found to ameliorate stress-induced anhedonia, reduce the associated elevations of hypothalamic corticotrophin-releasing factor (CRF) and restore the reductions in hypothalamic BDNF expression. Here we demonstrate chronic administration of captodiamine to have no significant effect on hypothalamic CRF expression through sigma-1 receptor agonism; however, both sigma-1 receptor agonism or 5-HT2c receptor antagonism were necessary to enhance BDNF expression. Regulation of BDNF expression by captodiamine was associated with increased phosphorylation of transcription factor CREB and mediated through sigma-1 receptor agonism but blocked by 5-HT2c receptor antagonism. The existence of two separate signalling pathways was confirmed by immunolocalisation of each receptor to distinct cell populations in the paraventricular nucleus of the hypothalamus. Increased BDNF induced by captodiamine was also associated with enhanced expression of synapsin, but not PSD-95, suggesting induction of long-term structural plasticity between hypothalamic synapses. These unique features of captodiamine may contribute to its ability to ameliorate stress-induced anhedonia as the hypothalamus plays a prominent role in regulating HPA axis activity.
Now, I looked long and hard and it seems basically impossible to get out of Europe. However, interestingly enough, it seems Desoxyn (Methamphetamine) raises Orexin while Dextroamphetamine does not. Methamphetamine, interestingly enough, is also a Sigma agonist:
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Psychiatry Res. 2016 May 30;239:9-11. doi: 10.1016/j.psychres.2016.02.059. Epub 2016 Feb 27.
Orexin-A level elevation in recently abstinent male methamphetamine abusers.
Abstract
Research has suggested that methamphetamine (METH) use influences orexin regulation. We examined the difference in orexin-A levels between METH abusers and healthy controls. Fasting serum orexin-A levels were measured in 35 participants who used METH in the preceding 3 weeks and 36 healthy controls. We found METH abusers had significantly higher orexin-A levels. No association was observed between orexin-A levels and METH use variables. Our results, consistent with prior preclinical evidence, showed that recent METH exposure is associated with increased orexin-A expression. Further investigation is required to determine whether orexin-A levels normalize after a longer term of abstinence.
I'm not quite sure what the implications of this would be. In the study "Immunocytochemical localization of the sigma(1) receptor in the adult rat central nervous system" (
https://www.ncbi.nlm...pubmed/10771347), they did find Sigma receptors in the following places:
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Diencephalon. Behind the olfactory bulb, the most intense immunostainings were detected in the hypothalamus (Fig. 6). Here, intense immunostaining was associated with perikarya of various sizes and with processes that were dispersed throughout the whole hypothalamus. In all of the brains examined, the highest staining intensities were associated with cells located in the supraoptic (Fig. 6A), the paraventricular (Fig. 6B), the arcuate (Fig. 6C) and the periventricular nuclei. In the thalamus, moderate to intense immunostaining was only detected in cells located in the habenula and the reticular nucleus, with the other thalamic subdivisions exhibiting faint if any immunostaining.
These are not located in the Lateral Hypothalamus, were most orexin neurons are located, but targeted those regions (Supraoptic, Paraventricular Nucleus, and the Arcuate) should enhance the signaling of Vasopressin, Oxytocin, and Growth hormone-releasing hormone. Vasopressin and Oxytocin seem to have positive effects on Orexin signaling, and GNRH directly promotes Slow Wave Sleep so perhaps that's why Sigma agonism seems to help in Hypothalamic neurogenesis. If someone knew of another reason why Sigma signaling seems to help, I'd highly appreciate the input.