μ-opioid receptor availability is associated with sex drive in human males

Abstract

The endogenous mu-opioid receptor (MOR) system modulates a multitude of social and reward-related functions, and exogenous opiates also influence sex drive in humans and animals. Sex drive shows substantial variation across humans, and it is possible that individual differences in MOR availability underlie interindividual of variation in human sex drive. We measured healthy male subjects’ (n = 52) brain’s MOR availability with positron emission tomography (PET) using an agonist radioligand, [11C]carfentanil, that has high affinity for MORs. Sex drive was measured using self-reports of engaging in sexual behaviour (sex with partner and masturbating). Bayesian hierarchical regression analysis revealed that sex drive was positively associated with MOR availability in cortical and subcortical areas, notably in caudate nucleus, hippocampus, and cingulate cortices. These results were replicated in full-volume GLM analysis. These widespread effects are in line with high spatial autocorrelation in MOR expression in human brain. Complementary voxel-based morphometry analysis (n = 108) of anatomical MR images provided limited evidence for positive association between sex drive and cortical density in the midcingulate cortex. We conclude that endogenous MOR tone is associated with individual differences in sex drive in human males.

Endogenous opioid release following orgasm in man: A combined PET-fMRI study

“…Furthermore, this finding accords well with human molecular imaging studies that have demonstrated endogenous opioid release following consumption of various rewards ranging from feeding to sociability (Manninen et al, 2017; Nummenmaa et al, 2018; Tuulari et al, 2017) and extends the role of the human MOR system to sexual pleasures. These data are also in line with recent PET data indicating MOR availability dependent individual differences in male sex drive, corroborating the role of ORs in modulating sexual motivation as well as sexual pleasure (Nummenmaa et al, 2022). It must nevertheless be noted due to the temporal resolution of PET we cannot conclusively state whether the presently observed opioid release reflects pleasure evoked by sexual stimulation, pleasure evoked by the orgasm or refractory activity in the post-orgasmic phase.…”

“…Finally, the result implied a central role of the thalamus in modulating sexual arousal. Taken together, these data yield, up to date, the most detailed picture of the functional and molecular brain basis of sexual arousal and climax in man, and support growing evidence for the general role of the endogenous opioid system in modulating the calmness—arousal axis in humans (Kantonen et al, 2020; Karjalainen et al, 2019; Nummenmaa et al, 2022).…”

“…The endogenous opioid system plays a key role in the mammalian reward circuit (e.g., Bozarth & Wise, 1981; DiFeliceantonio & Berridge, 2016; Nummenmaa & Tuominen, 2018), and accumulating evidence links the opioid receptor (OR) system in the regulation of sexual desire and arousal (e.g., Nummenmaa et al, 2022). Opiates are potent suppressors of sexual behaviors in both humans and animals (e.g., Pfaus & Gorzalka, 1987), and particularly μ-opioid receptor (MOR) agonists decrease human sexual desire and pleasure acutely and following chronic use (Birke et al, 2019).…”

“…Long-term endogenous opioidergic metabolism also contributes to individual differences in human sexual behaviour. One recent positron emission tomography (PET) study showed that MOR availability in cortical and subcortical areas, most notably in the caudate nucleus, hippocampus, and the cingulate cortices was positively correlated with sex drive in human males (Nummenmaa et al, 2022). This positive correlation is however surprising given the acute effects of exogenous opiate intake, but nevertheless corresponds well with findings on observed MOR availability in similar contexts, such as romantic and affiliative bonding in humans where higher MOR availability is consistently linked with seeking pleasure from social contacts (e.g., Turtonen et al, 2021).…”

Dopamine D2R and opioid MOR availability in autism spectrum disorder

“…MOR availability was measured with high-affinity agonist radioligand [11C]carfentanil [44] and D2R availability with high-affinity antagonist radioligand [11C]raclopride [45]. Radiotracer synthesis has been described previously [46, 47] Both radioligands were administered as a rapid bolus injection, after which the radioactivity in the brain was measured for 51 minutes. Injected doses were 245 ± 11 MBq for [11C]carfentanil and 254 ± 11 MBq for [11C]raclopride).…”