Effects of Ghrelin Administration on Dopamine and Effort
Status:
Recruiting
Trial end date:
2024-10-31
Target enrollment:
Participant gender:
Summary
Ghrelin is a stomach-derived hormone and the only known circulating peptide that stimulates
appetite. Animal studies have conclusively shown that ghrelin increases dopaminergic
neurotransmission and, thereby, enhances effort. However, similar evidence on the putative
role of ghrelin in humans is still lacking. Here, the investigators propose to conduct a
[11C]-raclopride PET/MR study after intravenous administration of ghrelin vs. saline in
healthy individuals. First, during an intake visit, the investigators will assess fasting
blood levels of hormones involved in appetitive behavior such as ghrelin, leptin, and
insulin. In addition, the investigators will conduct a set of tasks that have been associated
with dopamine function (i.e., effort and reinforcement learning). Second, the investigators
will assess the effects of intravenous administration of ghrelin on dopamine signaling using
a double-blind randomized cross-over design. To this end, participants will be infused with
ghrelin (vs. saline) while we determine dopamine release (via PET imaging) and assess
cerebral blood flow and functional connectivity at rest (via concurrent MR imaging).
Furthermore, the investigators will conduct an instrumental motivation task (IMT) where
participants have to exert physical effort to obtain rewards. Based on preclinical studies
and indirect evidence from human studies, the investigators hypothesize that ghrelin will
increase dopamine release in the striatum and that this will, in turn, lead to an increase in
the willingness to work for rewards. Moreover, the investigators expect that ghrelin-induced
dopamine release will be associated with an elevated tracking of reward utility in the
mesolimbic circuit during the IMT, which is known to be associated with response vigor.
Collectively, the proposed project would provide a unique resource to test an important link
between the gut and the brain in the regulation of appetitive behavior. If ghrelin were to
enhance effort expenditure for rewards via dopamine signaling in humans, then restoring
sensitivity to ghrelin might be the more promising therapeutic approach compared to
antagonizing the ghrelin receptor.