Acute citalopram has different effects on regional 5-HT synthesis in FSL, FRL, and SDP rats: an autoradiographic evaluation.
In this study, we measured the effect of an acute treatment of citalopram on 5-hydroxytryptamine (5-HT) synthesis in a genetic rat model of depression, the Flinders Sensitive Line (FSL) rats, their counterparts, the Flinders Resistant Line (FRL) rats, and outbred Sprague-Dawley (SPD) rats, using the alpha-[(14)C]methyl-l-tryptophan (alpha-MTrp) autoradiographic method. A comparison of 5-HT synthesis in the FSL rats treated with citalopram (FSL-CTP) and those treated with saline (FSL-SAL) indicate that citalopram reduces global 5-HT synthesis in the FSL rats, as well as in all the brain areas investigated. The reduced synthesis was also observed in the dorsal raphe (DR) nucleus and the median raphe (MR) nucleus. The comparison of the synthesis between the citalopram-treated SPD rats (SPD-CTP) and the saline-treated SPD rats (SPD-SAL) revealed a global increase of 5-HT synthesis in the SPD-CTP group, as well as an increase in some terminal areas, but a reduction in the DR and the MR. In contrast to the reduction throughout the brain in the FSL rats, the FRL rats treated with citalopram (FRL-CTP), when compared to the saline group (FRL-SAL), showed a global increase of 5-HT synthesis, as well as in most of the terminal areas and in the DR and the MR. The reduction of 5-HT synthesis throughout the brain in the FSL rats is likely, in part, a result of reported supersensitivity of the 5-HT(1A) receptors. Comparing changes in the SPD, FRL, and FSL rats treated with citalopram to their respective controls (saline-treated rats), the FSL rats treated acutely with citalopram were the only rats that exhibited lower 5-HT synthesis rates in all of the limbic areas, the basal ganglia, and the neocortices. This may be related to the pathophysiological basis of depressive characteristics in FSL rats. The citalopram treatment produced unexpected results in the FRL rats: 5-HT synthesis was elevated not only in most of the terminal areas, but also in the cell body areas, the DR and MR. The increase of 5-HT synthesis throughout the brain in the FRL rats is likely, in part, a result of the reported subsensitivity of the 5-HT(1A) receptors, and possibly other sites through which 5-HT synthesis could be controlled (e.g., 5-HT(1B)). In addition differences in intracellular signaling could be at least in part responsible for these differences.
Kanemaru
Kazuya
K
Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University Street, Montreal, Quebec H3A 2B4, Canada.
Hasegawa
Shu
S
Nishi
Kyoko
K
Diksic
Mirko
M
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001345:Autoradiography; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D011897:Random Allocation; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity; D014364:Tryptophan / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; C020774:alpha-methyltryptophan; D012701:Serotonin; D014364:Tryptophan