反激动剂
受体
兴奋剂
5-羟色胺能
药理学
5-羟色胺受体
血清素
5-HT1A受体
化学
内科学
全身给药
内分泌学
心理学
医学
生物
生物技术
体内
作者
Sven Melker Hagsäter,Robert Pettersson,Christopher Pettersson,Daniela Atanasovski,Jakob Näslund,Elias Eriksson
摘要
Abstract Background Though drugs binding to serotonergic 5-HT2A receptors have long been claimed to influence human anxiety, it remains unclear if this receptor subtype is best described as anxiety promoting or anxiety dampening. Whereas conditioned fear expressed as freezing in rats is modified by application of 5-HT2A–acting drugs locally into different brain regions, reports on the effect of systemic administration of 5-HT2A receptor agonists and 5-HT2A antagonists or inverse agonists on this behavior remain sparse. Methods We assessed the possible impact of systemic administration of 5-HT2A receptor agonists, 5-HT2A receptor inverse agonists, and a selective serotonin reuptake inhibitor (SSRI)—per se or in combination—on the freezing displayed by male rats when re-exposed to a conditioning chamber in which they received foot shocks 7 days earlier. Results The 5-HT2A receptor agonists psilocybin and 25CN-NBOH induced a reduction in conditioned fear that was countered by pretreatment with 5-HT2A receptor inverse agonist MDL 100907. While both MDL 100907 and another 5-HT2A receptor inverse agonist, pimavanserin, failed to impact freezing per se, both compounds unmasked a robust fear-reducing effect of an SSRI, escitalopram, which by itself exerted no such effect. Conclusions The results indicate that 5-HT2A receptor activation is not a prerequisite for normal conditioned freezing in rats but that this receptor subtype, when selectively over-activated prior to expression, exerts a marked fear-reducing influence. However, in the presence of an SSRI, the 5-HT2A receptor, on the contrary, appears to counter an anti-freezing effect of the enhanced extracellular serotonin levels following reuptake inhibition.
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