Hypothalamic dopaminergic receptor expressions in anorexia of tumor-bearing rats

Abstract

Our past microdialysis studies in ventromedial hypothalamic nucleus (VMN) and lateral hypothalamic area (LHA) of changes in dopamine concentrations in response to changes in food intake [characterized as feeding pattern (changes in meal number and size)] in anorexia of cancer show abnormal presynaptic dopaminergic neurotransmission. To determine postsynaptic receptor status, 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 D1- and D2-receptor mRNA expression in LHA and VMN were measured via RT-PCR. At anorexia, food intake decreased initially by a decrease in meal number, whereas a concurrent increase in meal size occurred for 24 h in an attempt to maintain food intake constant. Then meal size also decreased. At this time, D1- and D2-receptor mRNA expressions in LHA and VMN of TB vs. controls were significantly upregulated. Verification of D1- or D2-receptor changes to changes in meal number and size at anorexia was made by injection of intra-VMN or -LHA dopaminergic receptor antagonists. Intra-VMN D1-receptor antagonist (SCH-23390) in TB rats decreased food intake mainly via a decrease in meal size. Intra-VMN D2-receptor antagonist (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 D1-receptor antagonist in TB rats had no effect on food intake or feeding pattern. Intra-LHA D2-receptor antagonist in TB and in NTB free-feeding rats increased food intake via an increase in meal number. Our data provide evidence that postsynaptic dopaminergic receptor subtypes in the hypothalamus are involved in the regulation of meal size, meal number, and thus food intake in anorectic TB rats.