This study tested whether a 5-HT3 receptor antagonist could reverse the signs of precipitated opioid withdrawal. Rats were treated with either saline or morphine for 4 days. After the four days, half of the rats in each group received naloxone and half received saline. Each animal also received one of four doses of ondansetron (0, 1, 2 and 4 mg/kg i.p.). Administration of ondansetron to rats receiving naloxone after chronic morphine decreased the intensity of withdrawal signs such as increased defecation, jumping and wet-dog shakes, elevated the nociceptive threshold values which were decreased by precipitated withdrawal, but produced no change in urination, rectal temperature or salivation. The effects exhibited by ondansetron administration may be explained through interference of its 5-HT3 receptor antagonist activity with serotoninergic mechanisms involved in the regulation of these withdrawal symptoms. The use of this drug is thus suggested as a possible treatment of opioid withdrawal signs in heroin addicts.
"Animal evidence provides additional support for the notion that ondansetron can prevent signs of opioid withdrawal . Roychoudhury and Kulkarni (1996) found that 0.1Ymg/kg ondansetron prevented naloxone-induced opioid withdrawal in mice, and similar findings have been observed in rats (Hui et al., 1996; Pinelli et al., 1997). Previous work from our laboratory exploring genetic data on inbred strains of mice revealed that the gene most strongly associated with withdrawal severity was that for the 5-HT 3 receptor that is targeted by ondansetron. "
"One study found that it did not reduce the cravings of opiate addicted rodents , while another suggested that it could be useful in lowering the rate of relapse . Data reported by a group from Italy confirmed that naloxone precipitated withdrawal signs in morphine-dependent rats, and, that ondansetron prevented several of those signs . "
[Show abstract][Hide abstract] ABSTRACT: Introduction
Patients who are discharged following surgery on an oral opioid, and who have taken the drug for 2 or more weeks often experience withdrawal symptoms when they try to discontinue the drug.
Three weeks after discharge, a 44-year-old female patient decided to reduce her oxycodone (OxyContin®) dosage from 20 mg three times a day to 20 mg two times a day. She experienced severe withdrawal symptoms.
To assist her in withdrawing from the remainder of the drug, a protocol using ondansetron was developed.
After 10 days, the patient was opioid and withdrawal-symptom free.
Use of ondansetron along with tapering of the opioid was safe and effective in preventing further withdrawal symptoms. This case should stimulate research with a larger, more diverse population including those with both short-term and chronic opioid dependence.
"Thus, they were observed after the first injection (Time 1), the second injection (Time 2) and the third injection (Time 3). The following signs were observed: urine by weighing the liquid content absorbed in the paper dishes after feces removal, feces excretion, by weighing stools on paper dishes (Pinelli et al., 1997) and global withdrawal score (GWS hereafter). The GWS was calculated by attributing one point when each of the following signs was present: bwet dog shakesQ, salivation, jumping, head lift, mastication, teeth chattering, abnormal posture, cheek tremors, sniffing, jumps, escape attempts, vocalization when touched. "
[Show abstract][Hide abstract] ABSTRACT: In opiate-dependent rats previous studies showed that anaesthetic agents, such as chloral hydrate, midazolam and ketamine interfere with naloxone-precipitated opiate withdrawal. Each anaesthetic induces a specific pattern of interference, indicating that the interference is agent-dependent. In order to further investigate these effects and highlight a potential pharmacological basis of opiate withdrawal interference through anaesthetic agents, we hypothesized that anaesthetic-mediated interference of opiate withdrawal is also dose-dependent. Three groups of rats were compared in an experimental procedure of rapid withdrawal induction by an antagonist under anaesthesia using sub-anaesthetic dosage of midazolam, ketamine or saline. We observed that sub-anaesthetic dosage of ketamine, or midazolam, interferes significantly with opiate withdrawal expression. This brings arguments in favour of a pharmacological basis underlying rapid antagonists induction in opiate dependent rats.
Life Sciences 07/2005; 77(6):650-5. DOI:10.1016/j.lfs.2004.11.035 · 2.70 Impact Factor
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