title: Brain 5-HT synthesis in the Flinders Sensitive Line rat model of depression: an autoradiographic study.
abstract: Alterations of serotonin (5-HT) levels and serotonergic transmission have been associated with depression. 5-HT synthesis is an important factor of serotonergic neurotransmission that may also be altered in depression. Many studies of the relationships between brain serotonergic functions and affective disorders have been performed in different animal models. In this study, brain regional 5-HT synthesis was examined using the alpha-[(14)C]methyl-L-tryptophan (alpha-MTrp) autoradiographic method in a genetic rat model of depression, Flinders Sensitive Line (FSL) rats, and was compared to both the Flinders Resistant Line (FRL) rats and the control Sprague-Dawley (SD) rats. The plasma concentration of free tryptophan in the FSL rats was not significantly different (p > 0.05; ANOVA and post-hoc Bonferroni correction) when compared to that of the FRL and SD rats. The FSL rats had significantly lower 5-HT synthesis (one sample two-tailed t-test on the ratio) than both the FRL and SD rats (the mean ratios were 0.78 +/- 0.12 and 0.73 +/- 0.15, respectively). Overall, the 5-HT synthesis in the FRL rats was not significantly different (p > 0.05) from that in the SD rats (one sample two-tailed t-test on the ratio and the mean ratio was 0.93 +/- 0.13). Studies of individual brain structures, such as the raphe nuclei and their many terminal areas, including the nucleus accumbens, cingulate and frontal cortex, hippocampus, amygdala, and thalamus revealed significant reductions (typically 25-50%) in 5-HT synthesis in the FSL rats compared to the non-depressive FRL and SD rats. These results suggest that significantly reduced 5-HT synthesis in the raphe nuclei and limbic areas in FSL rats may contribute to their depressive features.
authors.affiliation: Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Que., Canada.
authors.forename: Shu
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nishi
authors.forename: Arata
authors.initials: A
authors.lastname: Watanabe
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
mesh_terms: D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000235:genetics; D002250:Carbon Radioisotopes; D003866:Depressive Disorder / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008032:Limbic System / Q000378:metabolism* / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism / Q000503:physiopathology; D011869:Radioligand Assay; D011903:Raphe Nuclei / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000096:biosynthesis*; D009435:Synaptic Transmission / Q000502:physiology; D014364:Tryptophan / Q000097:blood
chemical_list: D002250:Carbon Radioisotopes; D011985:Receptors, Serotonin; D012701:Serotonin; D014364:Tryptophan