Neural control of metabolism in healthy humans
Conditions
Interventions
Group 1: Each participant will come to the lab on two different days. Both testing days will be approximately identical and will last about 4.5 hours each. After the informed consent and the instructi
Sponsors
Max-Planck-Institut für Stoffwechselforschung
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: - No neurological diseases (e.g. stroke, epilepsy) - No diagnosed alcohol or drug addiction, incl. addiction to opioids/opiates (e.g. morphine, heroin) - no hypertension - No metabolic diseases (e.g. manifest diabetes mellitus) - No intake of medication that affects the metabolism, brain or immune system within the last 3 months (e.g. antidiabetics, psychotropic drugs, immunosuppressants, etc.) - No analgethic opiate intake - No mental illness within the last 3 months (e.g. depression, anxiety disorder) - No weight change > 5% in the last 3 months - No general contraindications regarding MRI measurements (e.g. metal implants) - Normal or normally corrected vision - Good German language skills - Women: not pregnant or breastfeeding
Exclusion criteria
Exclusion criteria: - Reported sleep periods or excessive motion during fMRI (> 3% volumes with framewise displacement > 1 mm) - Outlier in engagement in the effort (motivation) task - Problems with understanding instructions - BDI-II (Beck Depression Inventory) total score > 13, or item 9 score > 0 - Drop out (not completing both testing days)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The first aim of the project is to investigate the physiological effect of opioidergic neural pathways on the function of the paraventricular thalamus (PVT). Recent research in mice has shown that POMC neurons inhibit PVT neurons via mu-opioid receptors and also that this effect is most distinct in sated conditions and blocking these receptors results in an increase of PVT neuron activity (Minère et al., 2024). Based on these findings, we hypothesize that the Naloxone will increase the activity in the PVT. | — |
Secondary
| Measure | Time frame |
|---|---|
| The second aim of the project is to investigate the effect of Naloxone on the different aspects of motivated behavior and sugar appetite. To this end, 60 minutes after the intranasal application of Naloxone participants will undergo a reward-related computer task and will be offered a high sugar-containing dessert. Based on the actual findings in mouse studies, Naloxone reduces the intake of high sugar-containing foods in sated individuals (Minère et al., 2024). Given that sugar intake has a notable influence on the Nucleus accumbens (NAc), which plays an important role in learning from experiences or making cost-benefit trade-offs (Bouc et al., 2016; Cools et al., 2009), we can also suspect that Naloxone has an influence on motivational behavior. Therefore, we hypothesize that the application of intranasal Naloxone lowers the motivational behavior in sated participants. Furthermore, as a response to the consumption of high sugar-containing foods and the resulting increase in glucose levels, insulin is produced to maintain energic homeostasis. In addition, insulin itself has a downregulating effect on the mesoaccumbal circuit and its activity approximately 30 minutes after sugar consumption (Sallam and Borgland, 2021). The third aim of the project is to investigate whether the glucose-induced effects on motivated behavior and underlying neural processing after the intranasal application of Naloxone depend on individual differences in insulin sensitivity. To this end, we aim to recruit participants with a large variance of insulin sensitivity, assessed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Previous studies have shown that insulin resistance impairs the insulinergic regulation of motivated behavior and related neural processing. In insulin-resistant mice, the down-regulation of the mesoaccumbal circuit by insulin was suppressed (Figlewicz et al., 2006; Liu et al., 2013; Speed et al., 2011), and humans with reduced insulin sensiti | — |
Countries
Germany
Contacts
Public ContactMarc Tittgemeyer
Max-Planck-Institut für Stoffwechselforschung
Outcome results
None listed