5-HT increased histamine (HA) release from the anterior hypothalamus in anesthetized rats, and depolarized HA neurons. Since histaminergic tuberomammillary nucleus (TMN) receives 5-HT inputs from raphe´, we investigated whether SSRIs, mainstays in the treatment of depression, affect HA release. Citalopram (3–10 mg/Kg ip) significantly increased HA release from TMN of SD male rats (b.w.: 250 g). HA was determined by microdialysis and HPLC-fluorometric detection. In another set of experiments, rats were implanted with one probe in TMN, and one in nucleus basalis magnocellularis or nucleus accumbens. Citalopram (in Ringer) was perfused into the TMN at 2 ll/min. HA was measured in 15-min fractions collected from both probes. Spontaneous HA release from all regions was stable, ranging 0.05–0.08 pmol/15 min (N = 27). TMN perfusion with citalopram (1–100 lM) for 60 min significantly increased HA release up to 100% of basal value from all areas (P\0.05, ANOVA/Fisher’s test). Pretreatment with methysergide (10 lM), a 5-HT2 receptor antagonist, abolished the effect of citalopram, suggesting that citalopramactivates HAneurons by increasing extracellular levels of endogenous 5-HT. To learn whether SSRI effects depend on the histaminergic system, we used the tail suspension test in normal and histidine decarboxylase (HDC)-KO mice. Both citalopram (SSRI) and reboxetine (NSRI) reduced immobility in normal mice. Reboxetine also effectively reduced immobility in HDC-KO mice, which, surprisingly, failed to respond to citalopram. Similar results were observed in normal mice acutely depleted of neuronal histamine through ice cold injection of a-fluoromethyl-histidine, a suicide inhibitor of HDC. Thus HA plays important roles in mediating acute behavioural and neurochemical actions of citalopram.
|Titolo:||EFFECTS OF CITALOPRAM ON TAIL SUSPENSION TEST REQUIRE THE PRESENCE OF NEURONAL HISTAMINE|
|Anno di registrazione:||2010|
|Autori di Ateneo:|
|Autori:||L. Munari; M.B. Passani; N. Galeotti; P. Giannoni; H. Ohtsu; P. Blandina|
|Appare nelle tipologie:||1c - Abstract su rivista|
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