Animal models of the serotonin syndrome: A systematic review

Abstract

The serotonin syndrome (SS) is a potentially life-threatening disorder in humans which is induced by ingestion of an overdose or by combination of two or more serotonin (5-HT)-enhancing drugs. In animals, acute administration of direct and indirect 5-HT agonists also leads to a set of behavioral and autonomic responses. In the current review, we provide an overview of the existing versions of the animal model of the SS. With a focus on studies in rats and mice, we analyze the frequency of behavioral and autonomic responses following administration of 5-HT-enhancing drugs and direct 5-HT agonists administered alone or in combination, and we briefly discuss the receptor mediation of these responses. Considering species differences, we identify a distinct set of behavioral and autonomic responses that are consistently observed following administration of direct and indirect 5-HT agonists. Finally, we discuss the importance of a standardized assessment of SS responses in rodents and the utility of animal models of the SS in translational studies, and provide suggestions for future research.

Directly Observable Behavioral Effects of Lorcaserin in Rats

“…Drugs with agonist activity at 5-HT 2A receptors increase head twitching (Canal and Morgan, 2012). At doses larger than those producing head twitching, lorcaserin induced forepaw treading, an effect produced by drugs with agonist activity at 5-HT 1A receptors (Haberzettl et al, 2013). These results extend an earlier study (Thomsen et al, 2008) by confirming in vivo agonist properties of lorcaserin that appear to be mediated by 5-HT 2C receptors and by demonstrating other agonist properties of lorcaserin that appear to be mediated by 5-HT 2A and 5-HT 1A receptors.…”

Evidence of the dopamine-2 receptor mediated inhibition of the hypothalamic-pituitary-adrenal system; a rodent model of hypercortisolism in chronic neuropsychiatric disorders

“…Moreover, serotonin and noradrenaline and those pharmacologic agents, which influence their levels (monoamine oxidase inhibitors, tricyclics and selective serotonin reuptake inhibitors), play equally ambiguous [9,61,62] roles in the regulation of the HPA axis and mood disorders [61][62][63][64]. To clarify the mediation of their activity, and to shed light on their similarly unpredictable and dangerous side-effect spectrum [64,65] further studies are also required.…”

NBOMe Compounds: Systematic Review and Data Crunching of the Surface Web

“…Some drug fora (Quora.com, 2016;Psychonautwiki.org, 2016) provide instruction on how to use NBOMe, saying it is "not advised" to insufflate large amounts of NBOMe or to be taken in combination with selective serotonin reuptake inhibitors (SSRIs) and/or tricyclic antidepressants (TCAs), otherwise an inevitable serotonin toxidrome/syndrome will be imminent (Boyer and Shannon, 2005;Haberzettl et al, 2013;Psychonautwiki.org, 2016). Besides, NBOMe (particularly the 25i-NBOMe) can significantly elevate the blood pressure and exceptionally in individuals with already-established hypertension (Quora.com, 2016;Hare Krishna, 2016;Wood et al, 2015).…”

“…(Andreasen et al, 2015;Byard et al, 2016;Kueppers & Cooke, 2015;Lowe et al, 2015;Poklis et al, 2014;Rose et al, 2013;Shanks et al, 2015;Suzuki et al, 2014;Tang et al, 2014;Walterscheid et al, 2014). Serotonin toxidrome by itself can potentially produce acute toxicity involving metabolic acidosis, rhabdomyolysis, seizures, renal and liver failure, and disseminated intravascular coagulation (Bersani et al, 2014;Boyer & Shannon, 2005;Forrester, 2014;Haberzettl et al, 2013;Nikolaou et al, 2015;Wood et al, 2015).…”