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ABSTRACT: Background
The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving increasing attention as a promising obesity therapeutic. However, the neurobiological substrates mediating amylin's effects are not fully characterized. We postulated that amylin acts in the lateral dorsal tegmental nucleus (LDTg), an understudied neural processing hub for reward and homeostatic feeding signals.Methods
We used immunohistochemical and quantitative polymerase chain reaction analyses to examine expression of the amylin receptor complex in rat LDTg tissue. Behavioral experiments were performed to examine the mechanisms underlying the hypophagic effects of amylin receptor activation in the LDTg.Results
Immunohistochemical and quantitative polymerase chain reaction analyses show expression of the amylin receptor complex in the LDTg. Activation of LDTg amylin receptors by the agonist salmon calcitonin dose-dependently reduces body weight, food intake, and motivated feeding behaviors. Acute pharmacological studies and longer-term adeno-associated viral knockdown experiments indicate that LDTg amylin receptor signaling is physiologically and potentially preclinically relevant for energy balance control. Finally, immunohistochemical data indicate that LDTg amylin receptors are expressed on gamma-aminobutyric acidergic neurons, and behavioral results suggest that local gamma-aminobutyric acid receptor signaling mediates the hypophagia after LDTg amylin receptor activation.Conclusions
These findings identify the LDTg as a novel nucleus with therapeutic potential in mediating amylin's effects on energy balance through gamma-aminobutyric acid receptor signaling.
SUBMITTER: Reiner DJ
PROVIDER: S-EPMC5503810 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
Reiner David J DJ Mietlicki-Baase Elizabeth G EG Olivos Diana R DR McGrath Lauren E LE Zimmer Derek J DJ Koch-Laskowski Kieran K Krawczyk Joanna J Turner Christopher A CA Noble Emily E EE Hahn Joel D JD Schmidt Heath D HD Kanoski Scott E SE Hayes Matthew R MR
Biological psychiatry 20170110 11
<h4>Background</h4>The pancreatic- and brain-derived hormone amylin promotes negative energy balance and is receiving increasing attention as a promising obesity therapeutic. However, the neurobiological substrates mediating amylin's effects are not fully characterized. We postulated that amylin acts in the lateral dorsal tegmental nucleus (LDTg), an understudied neural processing hub for reward and homeostatic feeding signals.<h4>Methods</h4>We used immunohistochemical and quantitative polymera ...[more]