Chronic citalopram treatment elevates serotonin synthesis in flinders sensitive and flinders resistant lines of rats, with no significant effect on Sprague-Dawley rats.
The influence of citalopram on regional 5-hydroxytryptamine (serotonin, 5-HT) synthesis, one of the most important presynaptic parameters of serotonergic neurotransmission, was studied. Sprague-Dawley (SPD) rats were used as the controls, and Flinders Resistant Line (FRL) rats were used as auxiliary controls, to hopefully obtain a better understanding of the effects of citalopramon Flinders Sensitive Line (FSL; "depressed") rats. Regional 5-HT synthesis was evaluated using a radiographic method with a labelled tryptophan analog tracer. In each strain of rats, the animals were treated with citalopram (10 mg/(kg day)) or saline for 14 days. The groups consisted of between fourteen and twenty rats. There were six groups of rats with citalopram (CIT) and saline (SAL) groups in each of the strains (SPD-AL, SPD-IT, FRL-AL, FRL-IT, FSL-AL and FSL-IT). A two-factor analysis of variance was used to evaluate the effect of the treatment c., SPD-SAL relative to SPD-CIT) followed by planned comparisons to evaluate the effect in each brain region. In addition, the planned comparison with appropriate contrast was used to evaluate a relative effects in SPD relative to FSL and FRL, and FSL relative to FRL groups. A statistical analysis was first performed in the a priori selected regions, because we had learned, from previous work, that it was possible to select the brain regions in which neurochemical variables had been altered by the disorder and subsequent antidepressant treatments. The results clearly show that citalopram treatment does not have an overall effect on synthesis in the control SPD rats; there was no significant (p > 0.05) difference between the SPD-SAL and SPD-CIT rats. In "depressed" FSL rats, citalopram produced a significant (p < 0.05) elevation of synthesis in seventeen out of thirty-four regions, with a significant (p < 0.05) reduction in the dorsal and median raphe. In the FRL rats, there was a significant (p < 0.05) elevation in the synthesis in twenty-two out of thirty-four brain regions, with a reduction in the dorsal raphe. In addition to these regions magnus raphe was different in the SPD and FSL groups, but it was on the statistical grounds identified as an outlier. There were significant changes produced in the FSL and FRL rats in thirteen out of seventeen a priori selected brain regions, while in the SPD rats, citalopram produced significant changes in only four out of seventeen a priori selected regions. The statistical evaluation also revealed that changes produced by citalopram in the FSL and FRL rats were significantly greater than those in the SPD rats and that there was no significant difference between the effect produced in the FSL and FRL rats. The presented results suggest that in "depressed" FSL rats, the antidepressant citalopram elevates 5-HT synthesis, which probably in part relates to the reported improved in behaviour with citalopram.
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Quebec, Canada.
Kazuya
K
Kanemaru
Kyoko
K
Nishi
Shu
S
Hasegawa
Mirko
M
Diksic
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D015283:Citalopram / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004351:Drug Resistance / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013045:Species Specificity; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors