Chronic tryptophan deprivation attenuates gating deficits induced by 5-HT(1A), but not 5-HT₂ receptor activation.
Chronic tryptophan deprivation attenuates gating deficits induced by 5-HT(1A), but not 5-HT₂ receptor activation.
复制标题
慢性色氨酸剥夺会减弱 5-HT(1A) 诱导的门控缺陷，但不会减弱 5-HT 受体激活。
DOI：
10.1016/j.euroneuro.2012.10.009
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Bortolato,Marco
中科院分区：
文献类型：
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作者：
Stancampiano,Roberto;Frau,Roberto;Bini,Valentina;Collu,Maria;Carta,Manolo;Fadda,Fabio;Bortolato,Marco
The neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) exerts a multifaceted function in the modulation of information processing, through the activation of multiple receptor families. In particular, stimulation of 5-HT1Aand 5-HT2Areceptors leads to sensorimotor gating impairments and perceptual perturbations. Previous evidence has shown that chronic deprivation ofl-tryptophan (TRP), the precursor of 5-HT, results in marked reductions of 5-HT brain levels, as well as neuroplastic alterations in 5-HT1Aand 5-HT2Aexpression and/or signaling. Building on these premises, in the present study we tested whether a prolonged TRP deprivation may differentially impact the roles of these receptors in the regulation of the prepulse inhibition (PPI) of the acoustic startle reflex, a dependable index of gating. Male Sprague-Dawley rats were fed for 14 days with either a regimen with negligible TRP content (TR−) or the same diet supplemented of TRP (TR+). At the end of this schedule, rats were treated with the prototypical 5-HT1Areceptor agonist 8-OH-DPAT (62.5–250 μg/kg, subcutaneous, s.c.) or the 5-HT2receptor agonist DOI (0.25–1 mg/kg, s.c.). Notably, the PPI deficits induced by 8-OH-DPAT in TR− rats were significantly milder than those observed in their TR+ counterparts; these effects were fully prevented by the 5-HT1Aantagonist WAY-100135 (10 mg/kg, intraperitoneal). Conversely, TRP deprivation did not affect the PPI-disrupting properties of DOI. These findings suggest that prolonged 5-HT depletion attenuates the influence of 5-HT1A, but not 5-HT2receptors on sensorimotor gating, confirming the distinct mechanisms of these two targets in PPI regulation.
