[Abstract Title]. - Society for Neuroscience

Grants-in-Aid for Scientific Research from Japan Society for the Promotion of Science
18300128
Title: Bimodal effect of peripherally-administered ghrelin on the mesolimbic dopamine system
is dependent on the food consumption
Authors: Y. KAWAHARA 1 , *H. KAWAHARA 2 , F. KANEKO 1 , M. YAMADA 1 , Y. NISHI 1 ,
E. TANAKA 1 , A. NISHI 1 ;
1 Kurume Univ. Sch. Med., Kurume, Japan; 2 Dept Dent. Anesthesiol, Kyushu Dent. Col.,
Fukuoka 803-8580, Japan
Abstract: Ghrelin is a powerful orexigenic peptide released from the stomach that targets CNS
receptors to induce orexigenic behavior. The present study aimed to identify the neuronal
interactions that mediate the effects of peripherally-administered ghrelin on mesolimbic
dopaminergic neurons by intracerebral microdialysis. Peripheral administration of ghrelin
inhibited dopamine levels in the nucleus accumbens (NAc) when food was deprived following
ghrelin administration. This inhibitory effect was mediated through an increase in glutamatergic
inputs to the ventral tegmental area (VTA) that activate GABA interneurons and subsequent
inhibition of dopamine neurons via GABAA receptors. In contrast, when animals consumed food
following ghrelin administration, dopamine levels increased robustly. This stimulatory effect was
mediated through the increase in glutamatergic inputs that directly activate dopamine neurons via
NMDA receptors. Importantly, both the inhibitory and stimulatory effects of ghrelin required
activation of ghrelin receptors, growth hormone secretagogue 1 receptors (GHSRs), in the VTA,
presumably localized on GABA interneurons and dopamine neurons, respectively. When ghrelin
was injected locally into the VTA, dopamine release in the NAc increased regardless of food
consumption, supporting the local action of ghrelin on dopamine neurons. In addition, the role of
GHSRs in the VTA in the orexigenic effect of peripherally-administered ghrelin was
demonstrated. We conclude that peripherally-administered ghrelin, acting at GHSRs in the VTA,
induces bimodal effects on mesolimbic dopamine neurotransmission depending on the execution
of food consumption. A model of neuronal pathways based on the current data is discussed.
These findings propose a novel mechanism for ghrelin to regulate appetite and food
consumption.
Disclosures: Y. Kawahara, None; F. Kaneko, None; H. Kawahara , None; M. Yamada,
None; E. Tanaka, None; Y. Nishi, None; A. Nishi, None.
Poster
236. Neurotransmitter Release: Docking and Fusion
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 236.24/D24