Changes in the brain serotonin satiety system in transgenic rats lacking brain angiotensinogen.
In transgenic rats, TGR(ASrAOGEN)680, with reduced glial expression of angiotensinogen, changes in brain angiotensinogen are associated with reductions in serotonin (5-HT) content and/or 5-HT metabolism as determined in various brain regions, including the hypothalamus. These rats showed an anxious phenotype upon a first behavioural screen. The present study aimed to extend the search for functional consequences of changes in brain 5-HT with respect to feeding behaviour in these transgenic rats. In feeding experiments, rats were treated with the anorectic drug fenfluramine to probe for functional changes in the serotonergic satiety system. Fenfluramine (0.3 mg/kg, i.p.) reduced food intake in TGR(ASrAOGEN)680 rats whereas the minimal effective dose in wild-type rats was 3 mg/kg, i.p. Although, in the cortex, no differences were apparent in the expression of serotonin 5-HT(1A), 5-HT(1B), 5-HT(2C) receptor and 5-HT transporter mRNAs between TGR(ASrAOGEN)680 and wild-type rats, the expression of mRNAs for the 5-HT(2C) receptor and 5-HT transporter mRNA were significantly higher in the hypothalamus of TGR(ASrAOGEN)680 rats compared to wild-type rats. No differences were found in the mRNA levels for hypothalamic 5-HT(1A) and 5-HT(1B) receptors between TGR(ASrAOGEN)680 and wild-type rats. Taken together, these findings suggest that the transgenic effect on the brain 5-HT system is paralleled by functional changes of the serotonergic feeding system.
University of Nottingham, School of Veterinary Medicine and Science, Sutton Bonington Campus, Sutton Bonington, Leicestershire, UK. peter.voigt@nottingham.ac.uk
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Voigt
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Raasch
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Hörtnagl
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Bader
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Fink
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Jöhren
D000808:Angiotensinogen / Q000172:deficiency*; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000502:physiology; D005277:Fenfluramine / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000235:genetics; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
D012333:RNA, Messenger; D011985:Receptors, Serotonin; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D000808:Angiotensinogen; D005277:Fenfluramine; D012701:Serotonin