Journal
PHYSIOLOGICAL REPORTS
Volume 2, Issue 5, Pages -Publisher
WILEY
DOI: 10.14814/phy2.12004
Keywords
Brain slices; desensitization; extracellular recording; fat-rich diets; quinpirole
Categories
Funding
- Japan Society for the Promotion of Science (JSPS) [22500685, 25350166, 21249062, 23659529, 25670481, 25129708]
- Mishima Kaiun Memorial Foundation, Japan
- General Research Institute of Fukuoka University [106006]
- Ministry of Education, Culture, Sports, Science and Technology [21B-5]
- Nervous and Mental Disorder, and Health and Labor Science Research [21210301, KB220001]
- Ministry of Health, Labor and Welfare
- Central Research Institute for the Molecular Pathomechanisms of Epilepsy at Fukuoka University
- Fukuoka University [117016]
- Grants-in-Aid for Scientific Research [22500685, 25670481] Funding Source: KAKEN
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The ventral tegmental area (VTA) in the midbrain is important for food reward. High-fat containing palatable foods have reinforcing effects and accelerate obesity. We have previously reported that diet-induced obesity selectively decreased the spontaneous activity of VTA GABA neurons, but not dopamine neurons. The spontaneous activity of VTA dopamine neurons is regulated by D-2 autoreceptors. In this study, we hypothesized that obesity would affect the excitability of VTA dopamine neurons via D-2 autoreceptors. To examine this hypothesis, we compared D-2 receptor-mediated responses of VTA dopamine neurons between lean and obese mice. Mice fed on a high-fat (45%) diet and mice fed on a standard diet were used as obese and lean models, respectively. Brain slice preparations were made from these two groups. Spontaneous activity of VTA neurons was recorded by extracellular recording. Putative VTA dopamine neurons were identified by firing inhibition with a D-2 receptor agonist quinpirole, and electrophysiological criteria (firing frequency < 5 Hz and action potential current duration > 1.2 msec). Single-dose application of quinpirole (3 - 100 nmol/L) exhibited similar firing inhibition of putative VTA dopamine neurons between lean and obese mice. In stepwise application by increasing quinpirole concentrations of 3, 10, 30, and 100 nmol/L subsequently, quinpirole-induced inhibition of firing decreased in putative VTA dopamine neurons of obese mice compared with those of lean mice. In conclusion, high-fat diet-induced obesity attenuated D-2 receptor-mediated inhibition of putative VTA dopamine neurons due to the acceleration of D-2 receptor desensitization.
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