Striatal dopamine in the response of brain and liver unsaturated and saturated free fatty acids following administration of C75 in CD-1 mice.
In order to clarify the mechanism of action of cerulenin analog, C75, known to suppress feeding behavior, food intake was measured in adult CD-1 male mice n=5 per group, treated i.p. with 10 and 20mg/kg of C75. Animals in both treatment groups had significantly lower 24h food consumption rate relative to the control group injected with vehicle. Striatal monoamine neurotransmitters and striatal as well as liver long chain free fatty acids concentrations were subsequently evaluated in another group treated i.p. with 20mg/kg C75. Acute exposure to C75 at 20mg/kg led to approximately 50% increase in the striatal dopamine levels and a decrease in dopamine turnover for up to 24h following the injection. The concentration of serotonin remained unchanged. Concentration of saturated fatty acids in the liver and striatum did not change, while striatal unsaturated myristoleic acid (cis-9-tetradecenoic acid) levels were significantly higher as early as 2h post-injection and remained elevated at 24h post-injection. These preliminary data suggest a central regulatory role of unsaturated fatty acids under dopaminergic control in the C75-induced anorexia. Pharmacological alterations in fatty acid metabolism may prove beneficial in the treatment of obesity.
Binienda
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Division of Neurotoxicology, NCTR/FDA, Jefferson, AR 72079, USA. zbigniew.binienda@fda.hhs.gov
Ross
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Gough
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Riccio
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Kim
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Ali
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D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002569:Cerulenin / Q000031:analogs & derivatives; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018377:Neurotransmitter Agents / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013997:Time Factors
D019440:Anti-Obesity Agents; D015306:Biogenic Monoamines; D005229:Fatty Acids, Monounsaturated; D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D018377:Neurotransmitter Agents; D002569:Cerulenin; D012701:Serotonin; C014096:alpha-methylene gamma-butyrolactone; D015107:4-Butyrolactone; C054211:9-tetradecenoic acid; D004298:Dopamine