An assay of drug‐induced emesis in the squirrel monkey (Saimiri sciureus)

Abstract

Background Emesis has significant evolutionary value as a defense mechanism against ingested toxins; however, it is also one of the most common adverse symptoms associated with both disease and medical treatments of disease. The development of improved antiemetic pharmacotherapies has been impeded by a shortage of animal models. Methods The present studies characterized the responses of the squirrel monkey to pharmacologically diverse emetic drugs. Subjects were administered nicotine (0.032‐0.56 mg/kg), lithium chloride (150‐250 mg/kg), arecoline (0.01‐0.32 mg/kg), or apomorphine (0.032‐0.32 mg/kg) and observed for emesis and prodromal hypersalivation. Results Nicotine rapidly produced emesis and hypersalivation. Lithium chloride produced emesis with a longer time course without dose‐dependent hypersalivation. Arecoline produced hypersalivation but not emesis. Apomorphine failed to produce emesis or hypersalivation. Conclusions The squirrel monkey is sensitive to drug‐induced emesis by a variety of pharmacological mechanisms and is well‐positioned to examine antiemetic efficacy and clinically important side effects of candidate antiemetic pharmacotherapies.

Antiemetic Effects of Cannabinoid Agonists in Nonhuman Primates

“…Notably, D 9 -THC and mAEA were more effective at blocking nicotine-induced than LiCl-induced emesis. Both emetics have been shown to reliably produce emesis in several species, including the squirrel monkey, but may act via different mechanisms (Lee et al, 1978;Beleslin and Krstic, 1987;Billig et al, 2001;Parker et al, 2004Parker et al, , 2009Wooldridge and Kangas, 2019). Nicotine primarily acts at nicotinic receptors in the area postrema, or the "chemoreceptor trigger zone," of the central nervous system.…”

“…Both D 9 -THC and, to a lesser extent, mAEA also reduced the hypersalivation that accompanied nicotine-or LiCl-induced emesis, and consistent with the involvement of CB 1 receptor mechanisms, these cannabinergic effects could be blocked by rimonabant. Hypersalivation is thought to be a prodromal sign that often accompanies and worsens the subjective experience of emesis (Sanger and Andrews, 2006;Kenward et al, 2015;Wooldridge and Kangas, 2019). The ability of cannabinoid agonists to abate hypersalivation may therefore be a means of alleviating such distress and, consequently, reflects a desirable feature of their medicinal value.…”

“…Apparatus. A custom-designed dual-compartment observation chamber was used to monitor two subjects simultaneously (Wooldridge and Kangas, 2019). Two clear Plexiglas cubes (25 Â 25 Â 25 cm) separated by an opaque Plexiglas divider resided in a light-and soundattenuating ventilated enclosure (75 Â 60 Â 50 cm).…”

“…The antiemetic effects of D 9 -THC and mAEA were studied in subjects treated with emetic doses of nicotine and LiCl, both of which have been extensively used as emetic challenges in previous studies with shrews (Parker et al, 2004(Parker et al, , 2009 and ferrets (Billig et al, 2001;du Sert et al, 2012). The doses of nicotine (0.32 mg/kg) and LiCl (200 mg/kg), as well as the duration of observation periods (20 and 60 minutes, respectively) and D 9 -THC and mAEA pretreatment times (30 minutes), were based on previous studies of nicotine, LiCl, and cannabinoid agonists in squirrel monkeys (Justinova et al, 2013;Kangas et al, 2013Kangas et al, , 2016Leonard et al, 2017;Wooldridge and Kangas, 2019). First, the ability of D 9 -THC and mAEA to block nicotine-induced emesis and hypersalivation were determined by administering D 9 -THC (0.032 or 0.1 mg/kg), mAEA (3.2 or 10.0 mg/kg), or vehicle 30 minutes prior to treatment with saline or, in separate test sessions, a reliably emetic dose of nicotine (0.32 mg/kg).…”

Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence

“…Enteric nervous system and vagal nerves along with the myenteric and minor plexi regulate the peristalsis movement of the gut mucosa [72]. Abnormal contraction directly promotes the etiology of emesis via M receptor, D receptor, and GABA receptor [73]. In the number of preclinical and clinical studies, it was found that THC and CBD exert antiemetic action via inhibition of various neurotransmitter from the aforementioned receptors [74].…”