Naslov
Acute citalopram has different effects on regional 5-HT synthesis in FSL, FRL, and SDP rats : An autoradiographic evaluation

Autori
Kanemaru, Kazuya ; Hasegawa, Shu ; Nishi, Kyoko ; Dikšić, Mirko

Izvornik
Brain research bulletin (0361-9230) 77 (2008), 4; 214-220

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
tracer; depression model; autoradiography; antidepressant; α -[14C]methyl-l-tryptophan

Sažetak
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 -[14C]methyll- tryptophan (-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, aswell as in all the brain areas investigated. The reduced synthesiswas 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, aswell 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), whencompared 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-HT1A 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-HT1A receptors, and possibly other sites through which 5-HT synthesis could be controlled (e.g., 5-HT1B). In addition differences in intracellular signaling could be at least in part responsible for these differences.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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