Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats

Our past microdialysis studies in ventromedial hypothalamic nucleus (VMN) a nd lateral hypothalamic area (LHA) of changes in dopamine concentrations in response to changes in food intake [characterized as feeding pattern (chan ges in meal number and size)] in anorexia of cancer show abnormal presynapt ic dopaminergic neurotransmission. To determine postsynaptic receptor statu s, studies were done in tumor-bearing (TB) and non-tumor-bearing (NTB) free -feeding control rats while continuously measuring their food intake via a rat eater meter. When TB rats developed anorexia, TB and control rats were killed, and postsynaptic D-1- and D-2-receptor mRNA expression in LHA and V MN were measured via RT-PCR. At anorexia, food intake decreased initially b y a decrease in meal number, whereas a concurrent increase in meal size occ urred for 24 h in an attempt to maintain food intake constant. Then meal si ze also decreased. At this time, D-1- and D-2-receptor mRNA expressions in LHA and VMN of TB vs. controls were significantly upregulated. Verification of D-1- or D-2-receptor changes to changes in meal number and size at anor exia was made by injection of intra-VMN or -LHA dopaminergic receptor antag onists. Intra-VMN D-1-receptor antagonist (SCH-23390) in TB rats decreased food intake mainly via a decrease in meal size. Intra-VMN D-2-receptor anta gonist (sulpiride) in TB rats increased food intake via an increase in meal number and in NTB free-feeding rats by an increase in meal size. Intra-LHA D-1-receptor antagonist in TB rats had no effect on food intake or feeding pattern. Intra-LHA D-2-receptor antagonist in TB and in NTB free-feeding r ats increased food intake via an increase in meal number. Our data provide evidence that postsynaptic dopaminergic receptor subtypes in the hypothalam us are involved in the regulation of meal size, meal number, and thus food intake in anorectic TB rats.