5-HT2A/2c receptor and 5-HT transporter densities in mice prone or resistant to chronic high-fat diet-induced obesity:: a quantitative autoradiography study

The present study examined the density of 5-HT2A/2C receptors and 5-HT transporters in the brains of chronic high-fat diet-induced obese (cDIO) and obese-resistant (cDR) mice. Thirty-five male mice were used in this study. Twenty-eight mice were fed with a high-fat diet (40% of calories from fat) for 6 weeks and then classified as the cDIO (n = 8) or cDR (n = 8) mice according to the highest and lowest body weight gainers. Seven mice were placed on a low-fat diet (LF: 10% of calories from fat) and were used as controls. After 20 weeks of feeding, the sum of epididymal, perirenal, omental and inguinal fat masses was 9.3 +/- 0.3 g in the cDIO group versus 3.1 +/- 0.5 g in the cDR (p < 0.005) and 1.5 +/- 0.1 g in the LF (p < 0.001) groups. Using quantitative autoradiography techniques, the binding site densities of 5-HT2A/2C receptors and 5-HT transporters were measured in multiple brain sections of mice from the three groups. Most regions did not differ between groups but, importantly, the cDIO mice had a significantly higher 5-HT2A/2C binding density in the anterior olfactory nucleus and ventromedial hypothalamic nucleus (VMH) compared to the cDR and LF mice (+39% and + 47%, p = 0.003 and 0.045, respectively), whereas the latter two groups did not differ. The density of 5-HT2A/2C receptors in the VMH was associated with total amount of fat mass (r= 0.617, p = 0.032). On the other hand, the cDR mice had significantly lower 5-HT transporter binding than the cDIO and LF mice, respectively, in the nucleus accumbens ( -44%, -38%, both p < 0.02), central nucleus of the amygdaloid nucleus ( - 40%, - 44%, p = 0.003 and 0.009), and olfactory tubercle nucleus ( - 42%, - 42%, both p = 0.03). In conclusion, this study has demonstrated differentially regulated levels of the 5-HT2A/2C receptor and 5-HT transporter in specific brain regions of the cDIO and cDR mice. It provides neural anatomical bases by which genetic variability in 5-HT2A/2C receptors and 5-HT transporter may influence satiety and sensory aspects of energy balance. (C) 2004 Elsevier B.V. All rights reserved.