I’Anson H, Jethwa PH, Tanna GA, Pattinson LM, Ebling FJP (2007) Histaminergic regulation of energy homeostasis in the Siberian hamster. Neuroscience 2007 Abstracts 629.17/YY20. Society for Neuroscience, San Diego, CA.
Summary: We tested the hypothesis that posterior hypothalamic histaminergic (HA) activity regulates energy homeostasis in the Siberian hamster during long day (breeding season) photoperiods. Adult male Siberian hamsters were given bilateral injections of the retrogradely transported ribosomal toxin, saporin, conjugated to orexin-B receptor antibody (OXSAP, 200 nl, 92 ng/ul) into the posterior hypothalamus (PH) to selectively destroy HA neurons, the majority of which possess orexin-B receptors. Controls were injected with unconjugated saporin (sham). Metabolic rate (VO2 ml/kg0.75/h), ingestive behavior and locomotor activity were monitored using the comprehensive lab animal monitoring system (CLAMS, Columbus instruments). Body weight was significantly decreased by day 12 post-surgery in OXSAP compared with sham hamsters and remained significantly lower throughout the 5 month study, even though food intake was comparable between groups. At 3 months post-surgery, OXSAP food intake was significantly higher in the dark (p< 0.05) and significantly lower in the light phase (p<0.05), but not different overall between groups. In addition, the frequency of feeding bout tended to be lower during dark and light phases compared with sham hamsters (p=0.07). Lower body weight with no overall change in food intake suggests an increase in energy expenditure in the OXSAP hamsters. Consistent with this interpretation, locomotor activity in OXSAP hamsters tended to be higher during the dark phase (p=0.09), but not in the light phase. In addition, metabolic rate was significantly higher during the first two hours of the dark phase compared with sham hamsters (p<0.05), and tended to be higher during the entire dark phase (p=0.08). During a second CLAMS study (4 months post-surgery), metabolic rate was monitored following injection of an H3 receptor antagonist (thioperamide, 30 mg/kg, ip) as a probe to determine if any significant HA cell loss had occurred. Metabolic rate was significantly lower during the first 2 hours after thioperamide in sham hamsters, but not in OXSAP hamsters, suggesting that HA regulation of energy balance had been compromised by the OXSAP lesion. Immunohistochemical results confirmed 63-96% loss of HDC-immunoreactivity in magnocellular neurons of the posterior hypothalamus in the OXSAP group. These data support the hypothesis that posterior hypothalamic HA neuron activity modulates metabolic activity during the breeding season in the Siberian hamster, although it is likely that ablation of additional neuronal phenotypes which express orexin-B (e.g. MCH) may contribute to the observed metabolic effects.
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