Extracellular Hypothalamic Monoamines Measured by In Vivo Microdialysis in a Rat Model of Dietary Fat‐Induced Obesity

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Abstract
We tested two hypotheses about monoamine neurotransmitters in two strains of rats that differ in their sensitivity to obesity when eating a high‐fat diet; 1) that the concentrations of norepinephrine and serotonin and of their metabolites differ in the extracellular fluid of tlie ventromedial hypothalamus of conscious, unrestrained Osborne‐Mendel and S 5B/PI rats, and 2) that these monoamines are altered differently between strains by a high‐fat diet. The monoamines were measured by HPLC in dialysate collected by in vivo microdialysis in rats eating a semisyntlietic low‐fat diet (10% of kcal as fat) and again after either two or seven days of eating a high‐fat diet (56 % of kcal as fat). Norepinephrine, serotonin (5‐HT), and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) were lower in Osborne‐Mendel rats than in S 5BR1 rats eating the low‐fat diet. Norepinephrine and serotonin both increased in Osborne‐Mendel rats with the onset of tlie high‐fat diet so that Osborne‐Mendel and S 5B/PI rats no longer differed in these neurotransmitters. By day 7 of high‐fat feeding, the concentrations of 3‐methoxy‐4‐hydroxyplienylglycol (MHPG), 5‐HIAA and the 5‐HIAA/5‐HT ratio rose in both strains. Ambient extracellular monoamines in the medial hypothalamus are lower in Osborne‐Mendel rats than in S 5B/PI rats and the response of these catecholamines to dietary fat was greater in Osborne‐Mendel rats than in S 5B/PI rats.