NeuropharmacologyResearch PaperPeripherally administered ghrelin induces bimodal effects on the mesolimbic dopamine system depending on food-consumptive states
Section snippets
Animals
Male Wistar rats (270–340 g, Kyudo, Tosu, Japan) were used. The rats were maintained at 23±2 °C under a 12-h light/dark cycle with free access to food and water. Two rats were housed in one home cage till the surgery. All rats used in this study were handled in accordance with the Guide for the Care and Use of Laboratory Animals as adopted and promulgated by the US National Institutes of Health, and the specific protocols were approved by the Committee for Animal Experimentation, Kurume
Effect of peripherally administered ghrelin followed by food removal on the dialysate content of dopamine in the NAc
I.v. administration of ghrelin (3 nmol/0.2 mL) in the absence of food reduced the extracellular dopamine levels in the NAc to about 60% of basal levels (Fig. 1A). The statistically significant decrease lasted for 1 h after ghrelin administration (F9,45=4.01, P<0.0001). The animals displayed walking and rearing for a short period after ghrelin administration and maintained the sleeping position throughout the course of the experiment. In control rats received i.v. administration of saline (0.2
Discussion
The present study demonstrates that peripherally administered ghrelin affects the mesolimbic dopamine system differentially depending on the state of food consumption. Under conditions without food consumption, ghrelin inhibits dopamine neurons in the VTA and dopamine release in the NAc. The inhibitory effect of ghrelin is mediated through interactive actions of GHSRs, NMDA receptors and GABAA receptors in the VTA. In contrast, under conditions with food consumption, ghrelin stimulated dopamine
Acknowledgments
This work was supported by the Kurume University School of Medicine and Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (19592308 and 18300128). We wish to thank Professor Masayasu Kojima for his comments and Professor Tatsuyuki Kakuma for advice on the statistical analysis.
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