Effects of ondansetron administration on opioid withdrawal syndrome observed in rats

Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milano, Lombardy, Italy
European Journal of Pharmacology (Impact Factor: 2.68). 12/1997; 340(2-3):111-9. DOI: 10.1016/S0014-2999(97)01349-6
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of psychoactive drugs is a wide spread behaviour in human societies. The systematic use of a drug requires the establishment of different drug use-associated behaviours which need to be learned and controlled. However, controlled drug use may develop into compulsive drug use and addiction, a major psychiatric disorder with severe consequences for the individual and society. Here we review the role of the serotonergic (5-HT) system in the establishment of drug use-associated behaviours on the one hand and the transition and maintenance of addiction on the other hand for the drugs: cocaine, amphetamine, methamphetamine, MDMA (ecstasy), morphine/heroin, cannabis, alcohol, and nicotine. Results show a crucial, but distinct involvement of the 5-HT system in both processes with considerable overlap between psychostimulant and opioidergic drugs and alcohol. A new functional model suggests specific adaptations in the 5-HT system, which coincide with the establishment of controlled drug use-associated behaviours. These serotonergic adaptations render the nervous system susceptible to the transition to compulsive drug use behaviours and often overlap with genetic risk factors for addiction. Altogether we suggest a new trajectory by which serotonergic neuroadaptations induced by first drug exposure pave the way for the establishment of addiction.
    Behavioural brain research 04/2014; DOI:10.1016/j.bbr.2014.04.007 · 3.39 Impact Factor
  • Source
    [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. Case Report 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. Method To assist her in withdrawing from the remainder of the drug, a protocol using ondansetron was developed. Results After 10 days, the patient was opioid and withdrawal-symptom free. Conclusion 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.
    12/2012; 1(1). DOI:10.1007/s40122-012-0004-5
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute alcohol intoxication causes cellular changes in the brain that last for hours, while chronic alcohol use induces widespread neuroadaptations in the nervous system that can last a lifetime. Chronic alcohol use and the progression into dependence involve the remodeling of synapses caused by changes in gene expression produced by alcohol. The progression of alcohol use, abuse, and dependence can be divided into stages, which include intoxication, withdrawal, and craving. Each stage is associated with specific changes in gene expression, cellular function, brain circuits, and ultimately behavior. What are the molecular mechanisms underlying the transition from recreational use (acute) to dependence (chronic)? What cellular adaptations result in drug memory retention, leading to the persistence of addictive behaviors, even after prolonged drug abstinence? Research into the neurobiology of alcoholism aims to answer these questions. This chapter will describe the molecular adaptations caused by alcohol use and dependence, and will outline key neurochemical participants in alcoholism at the molecular level, which are also potential targets for therapy.
    Handbook of Clinical Neurology 01/2014; 125C:89-111. DOI:10.1016/B978-0-444-62619-6.00006-9