VMN hypothalamic dopamine and serotonin in anorectic septic rats

During sepsis, catabolism of proteins and associated changes in plasma amin o acids occur. Tryptophan and tyrosine, and their derivatives serotonin (5- HT) and dopamine (DA), influence hypothalamic feeding-related areas and are associated with the onset of anorexia- We hypothesized that anorexia of se psis is associated with changes in serotonin and dopamine in-the ventromedi al nucleus (VMN) of the hypothalamus. The aim of this study was to test our hypothesis by measuring intra-VMN changes of these two neurotransmitters a t the onset of anorexia during sepsis. Fischer 344 male rats had an intrace rebral guide cannula stereotaxically implanted into the VMN. Ten days later , in awake, overnight-food-deprived rats, a microdialysis probe was inserte d through the in situ VMN cannula. Two hours thereafter, serial baseline se rotonin and dopamine concentrations were measured. Then cecal ligation and puncture to induce sepsis or a control laparotomy was performed under isofl urane anesthesia. VMN microdialysis samples were serially collected every 3 0 min for 8 h after the surgical procedure to determine 5-HT and DA changes in response to sepsis. During the hypermetabolic response to sepsis, a str ong association occurred between anorexia and a significant reduction of VM N dopamine concentration (P < 0.05; constant rate of dopamine decrease in t he Study group of 0.99 pg per 2 h); no changes occurred in 5-HT in associat ion with anorexia of sepsis. Six hours after operation, a single meal was o ffered for 20 min to assess the response of neurotransmitters to food inges tion. Food intake was minimal in anorectic septic rats (mean size of the af ter food-deprived meal in the Septic group was 0.03 +/- 0.01 g, that of the Control group was 1.27 +/- 0.14 g; P = 0.0001), while Control rats demonst rated anticipated changes in neurotransmitters in response to eating. We co nclude that the onset of anorexia in septic rats is associated with a reduc tion in VMN dopamine.