Implication of 5-HT(2B) receptors in the serotonin syndrome.

نویسندگان

  • Silvina Laura Diaz
  • Luc Maroteaux
چکیده

The serotonin (5-HT) syndrome occurs in humans after antidepressant overdose or combination of drugs inducing a massive increase in extracellular 5-HT. Several 5-HT receptors are known to participate in this syndrome in humans and animal models. The 5-HT(2B) receptor has been proposed as a positive modulator of serotonergic activity, but whether it is involved in 5-HT syndrome has not yet been studied. We analyzed here, a putative role of 5-HT(2B) receptors in this disorder by forced swimming test (FST) and behavioral assessment in the open field. In FST, genetic (5-HT(2B)(-/-) mice) or pharmacological (antagonist RS127445 at 0.5 mg/kg) ablation of 5-HT(2B) receptors facilitated selective 5-HT reuptake inhibitors (SSRI)-induced increase of immobility time as well as expression of other symptoms related to 5-HT syndrome like hind limb abduction and Straub tail. Increase in immobility was also developed in FST by both wild type (WT) and 5-HT(2B)(-/-) mice after the administration of 5-HT(1A), 5-HT(2A) or 5-HT(2C) receptor agonists, 8-OH-DPAT (5 mg/kg), DOI (1 mg/kg), or WAY161503 (5 mg/kg), respectively. In contrast, the 5-HT(2B) receptor agonist BW723C86 (3 mg/kg) or 5-HT(1B) receptor agonist CGS12066A (2 mg/kg) decreased immobility time in both genotypes. The 5-HT syndrome induced by fluoxetine at high doses was blocked in WT and 5-HT(2B)(-/-) mice by administration of 5-HT(1A) and 5-HT(2C) receptor antagonists (WAY100635 0.5 mg/kg and SB242084 0.5 mg/kg) but not by the 5-HT(2A) receptor antagonist MDL100907 (1 mg/kg). By behavioral assessment, we confirmed that 5-HT(2B)(-/-) mice were more prone to develop 5-HT syndrome symptoms after administration of high dose of SSRIs or the 5-HT precursor 5-Hydroxytryptophan, 5-HTP, even if increases in 5-HT plasma levels were similar in both genotypes. This evidence suggests that the presence of 5-HT(2B) receptors hinders acute 5-HT toxicity once high levels of 5-HT are attained. Therefore, differential agonism/antagonism of 5-HT receptors should be considered in the search of therapeutic targets for treating this serious disorder.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Modified receptor internalization upon coexpression of 5-HT1B receptor and 5-HT2B receptors.

Serotonin 5-HT(2B) receptors are often coexpressed with 5-HT(1B) receptors, and cross-talk between the two receptors has been reported in various cell types. However, many mechanistic details underlying 5-HT(1B) and 5-HT(2B) receptor cross-talk have not been elucidated. We hypothesized that 5-HT(2B) and 5-HT(1B) receptors each affect the others' signaling by modulating the others' trafficking. ...

متن کامل

Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine-induced hyperlocomotion and 5-HT release in vivo and in vitro.

The "club drug" 3,4-methylenedioxymethamphetamine (MDMA; also known as ecstasy) binds preferentially to and reverses the activity of the serotonin transporter, causing release of serotonin [5-hydroxytryptamine (5-HT)] stores from nerve terminals. Subsequent activation of postsynaptic 5-HT receptors by released 5-HT has been shown to be critical for the unique psychostimulatory effects of MDMA. ...

متن کامل

Serotonin receptor 5-HT2B mediates serotonin-induced mechanical hyperalgesia.

Serotonin [5-hydroxytryptamine (5-HT)] released from mast cells or platelets in peripheral tissues is one of the important inflammatory mediators in pain and hyperalgesia. The involvement of 5-HT in pain is complex because it could inhibit or facilitate nociceptive transmission, reflecting the presence of multiple 5-HT subtype receptors on peripheral and central nociceptors. The present study a...

متن کامل

Regulation of Appetite: Role of Serotonin and Hypothalamus

Serotonin (5-HT), a mono-aminergic neurotransmitter is biochemically derived from tryptophan and is mainly found in gastrointestinal tract, platelets and central nervous system of animals. Serotonin (5-HT) in coordination with hypothalamus plays an important role in the CNS control of appetite, eating behavior, and energy balance and body weight. It has a special role in control of carbohydrate...

متن کامل

Effect of cisplatin treatment on the response to serotonin

  Although cisplatin is one of the most effective cancer drugs which is widely used in the treatment of various neoplasms, its side effects, especially vomiting may limit its use. It has been demonstrated that cytotoxic drugs lead to a sudden release of serotonin (5-HT). The following study was performed to determine the possible interactions of cisplatin with 5-HT receptors. In this study, the...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Neuropharmacology

دوره 61 3  شماره 

صفحات  -

تاریخ انتشار 2011