Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

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anacleta
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Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

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Published: 25 August 2021

Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling

Stephen X. Zhang, Andrew Lutas, Shang Yang, Adriana Diaz, Hugo Fluhr, Georg Nagel, Shiqiang Gao & Mark L. Andermann
Nature (2021)

Abstract

Transient neuromodulation can have long-lasting effects on neural circuits and motivational states1,2,3,4. Here we examine the dopaminergic mechanisms that underlie mating drive and its persistence in male mice. Brief investigation of females primes a male’s interest to mate for tens of minutes, whereas a single successful mating triggers satiety that gradually recovers over days5. We found that both processes are controlled by specialized anteroventral and preoptic periventricular (AVPV/PVpo) dopamine neurons in the hypothalamus. During the investigation of females, dopamine is transiently released in the medial preoptic area (MPOA)—an area that is critical for mating behaviours. Optogenetic stimulation of AVPV/PVpo dopamine axons in the MPOA recapitulates the priming effect of exposure to a female. Using optical and molecular methods for tracking and manipulating intracellular signalling, we show that this priming effect emerges from the accumulation of mating-related dopamine signals in the MPOA through the accrual of cyclic adenosine monophosphate levels and protein kinase A activity. Dopamine transients in the MPOA are abolished after a successful mating, which is likely to ensure abstinence. Consistent with this idea, the inhibition of AVPV/PVpo dopamine neurons selectively demotivates mating, whereas stimulating these neurons restores the motivation to mate after sexual satiety. We therefore conclude that the accumulation or suppression of signals from specialized dopamine neurons regulates mating behaviours across minutes and days.

https://www.nature.com/articles/s41586-021-03845-0

Video https://youtube.com/watch?v=2K5d1j3Gg04

Media https://medicalxpress.com/news/2021-08- ... -mice.html
cdraham
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

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in which relation does this stand with pssd?
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anacleta
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

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The authors say that their results may help to understand why SSRIs cause sexual dysfunction such as lowered libido and in the references there is the review by Bala et al on pssd, so it will be interesting to understand this from the full text.
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anacleta
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

Unread post by anacleta »

Image

Anteroventral and preoptic periventricular (AVPV/PVpo)
Medial preoptic area (mPOA)
Nucleus accumbens (NAc)
Cyclic adenosine monophosphate (cAMP)
Brain food
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

Unread post by Brain food »

I found another recently released article that could offer a possible explanation of PSSD. I would like to make a new post about it on this forum but I don’t know how to. While I don’t think that sunlight can cure PSSD, it’s possible that the SSRIs screw up the p53 protein mechanism described in this article. This could explain why many people with PSSD, including myself, have low testosterone levels. Under this theory the problem with PSSD begins in the skin. The skin around the genitals isn’t signaling to the nervous system correctly and this explains loss of pleasure from genital stimulation and low libido. If you search for p53 and antidepressants or SSRIs on Google you will find some articles that show a connection, mostly in regards to cancer research. This research is still very preliminary and it’s too early to draw conclusions. Also, even if a problem with the p53 protein is discovered in PSSD patients that doesn’t mean there’s currently a way to treat it. Anyways, here’s the article and the summary of the findings.

Skin exposure to UVB light induces a skin-brain-gonad axis and sexual behavior
https://www.cell.com/cell-reports/fullt ... ctitle0010

Ultraviolet (UV) light affects endocrinological and behavioral aspects of sexuality via an unknown mechanism. Here we discover that ultraviolet B (UVB) exposure enhances the levels of sex-steroid hormones and sexual behavior, which are mediated by the skin. In female mice, UVB exposure increases hypothalamus-pituitary-gonadal axis hormone levels, resulting in larger ovaries; extends estrus days; and increases anti-Mullerian hormone (AMH) expression. UVB exposure also enhances the sexual responsiveness and attractiveness of females and male-female interactions. Conditional knockout of p53 specifically in skin keratinocytes abolishes the effects of UVB. Thus, UVB triggers a skin-brain-gonadal axis through skin p53 activation. In humans, solar exposure enhances romantic passion in both genders and aggressiveness in men, as seen in analysis of individual questionaries, and positively correlates with testosterone level. Our findings suggest opportunities for treatment of sex-steroid-related dysfunctions.
Brain food
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

Unread post by Brain food »

Here’s an earlier article from 2004 where Japanese researchers found a relationship between p53 and low testosterone in mice. I only found a summary of the article on researchgate.net. If someone can find the full article for free and post it that would be great.

Penile apoptosis in association with p53 under lack of testosterone

https://www.researchgate.net/publicatio ... stosterone

It is known that testosterone deficiency induces apoptosis in the prostate and that p53 protein is involved in this apoptosis. Therefore, p53 protein may also be involved in apoptosis induction in a testosterone-deficient state in the penis. In this study, we investigated whether castration and chemical castration induce apoptosis at penile tissue in rats, and whether p53 protein is involved in this apoptosis. Male SD rats aged 8 weeks were divided into four groups: 1) the Control group; 2) the Castration group; 3) the Estrogen group, in which rats received betaestradiol 17-(beta-D-glucuronide) injection of 500 microg/body/day; and 4) the LH-RH group, in which rats received LH-RH analogue (leuprorelin acetate) injection of 2 mg/kg. The rats were sacrificed after treatment on days 1, 3, 5, 14, and 28 by cervical dislocation. Apoptotic cells and p53 protein-positive cells were observed on the 5th day after treatment and thereafter in all castration, estrogen, and LH-RH groups. These findings showed that both castration and chemical castration induced p53 protein in vascular endothelial cells in the corpus cavernosus during the process of losing testosterone. It was also suggested that in such states, apoptosis is induced in vascular endotherial cells in the corpus cavernosus.
Impermanence
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

Unread post by Impermanence »

Interesting... In this recent article the speak about the P53 and its involving in libido

'Skin exposure to UVB light induces a skin-brain-gonad axis and sexual behavior'
Roma Parikh Eschar Sorek Shivang Parikh Ruth Percik Aron Weller Carmit Levy 27
Show all authors
https://www.cell.com/cell-reports/fullt ... 21)01013-5
Brain food
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

Unread post by Brain food »

@Impermanece and @anacleta do you know how I can make a new post on this forum to write about the University of Tel Aviv study that I mentioned above?
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guacamo
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

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Very interesting article. Extrapolating information content from this could result in an idea that it's 5-HT7 receptor that mediates this pro-sexual effect, as it both increases cAMP and protein kinase A and has numerous expression in hypothalamus, on the other hand when something like this pops up, it creates whole tree with lot of branches that need to be studied to understand this topic better, most of the time it is a dead end by either lacking studies on said receptor (as it is with 5-HT7, because there is no strong selective 5-HT7 ligand ) or has dual functionality, which also is the case here as 5-HT7 exist in raphe nuclei (presynaptic receptor) and in other parts of the brain as post-synaptic receptor, the consequence of this is conflicting studies, as one receptor type can have higher or lower EC50 value, which result that in one study it produces certain effect and in another it affects the same thing but in an opposite way.
Brain food
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Re: Hypothalamic dopamine neurons motivate mating through persistent cAMP signalling. 2021

Unread post by Brain food »

Here’s an article that summarized this study pretty well and explains why it may lead to treatments for the sexual side effects of antidepressants.

https://www.genengnews.com/news/sex-dri ... mechanism/
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