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Ondansetron inhibits a behavioural consequence of withdrawing from drugs of abuse
B Costall1, B J Jones, M E Kelly
1Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, U.K.
Abstract:
The ability of the selective 5-HT3 receptor antagonist ondansetron to influence the behavioural consequences of withdrawal from chronic treatment with ethanol, nicotine or cocaine was investigated in the light/dark exploration test in the mouse and social interaction test in the rat. In both tests acute and chronic (7 days) treatments with ondansetron (0.01-1.0 microgram.kg-1 IP) disinhibited suppressed behaviour; withdrawal from chronic treatment (0.1 mg/kg IP b.i.d.) did not exacerbate the behavioural suppression. Chronic treatment for 14 days with ethanol (8% w/v in the drinking water), nicotine (0.1 mg/kg b.i.d.) or cocaine (1.0 mg/kg b.i.d.) released suppressed behaviour in the mouse and rat tests. Behavioural suppression was increased following withdrawal from ethanol, nicotine and cocaine. The administration of ondansetron (0.01 mg/kg IP b.i.d.) during the period of ethanol, nicotine and cocaine withdrawal prevented the exacerbation in suppressed behaviour. It is concluded that ondansetron potently reduces behavioural suppression during acute and chronic treatments in the rodent models, does not cause a rebound exacerbation of behavioural suppression following withdrawal, and is a highly effective inhibitor of the increased behavioural suppression following withdrawal from the drugs of abuse: ethanol, nicotine and cocaine.
Insights
Ondansetron, a 5-HT3 antagonist, reduces behavioral suppression during drug withdrawal from ethanol, nicotine, and cocaine. It effectively prevents withdrawal-induced behavioral changes without causing rebound effects.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Substance abuse withdrawal often leads to significant behavioral changes.
- Selective 5-HT3 receptor antagonists are being investigated for their potential therapeutic effects.
Purpose of the Study:
- To investigate the efficacy of ondansetron in mitigating behavioral consequences of withdrawal from ethanol, nicotine, and cocaine.
- To assess ondansetron's effects on behavior during acute and chronic drug treatments and withdrawal periods.
Main Methods:
- Utilized the light/dark exploration test in mice and the social interaction test in rats.
- Administered ondansetron acutely and chronically to assess its direct effects and during withdrawal phases from ethanol, nicotine, and cocaine.
Main Results:
- Ondansetron (0.01-1.0 microgram/kg) disinhibited suppressed behavior during acute and chronic treatments.
- Withdrawal from chronic ethanol, nicotine, or cocaine exacerbated behavioral suppression.
- Ondansetron (0.01 mg/kg) administration during withdrawal prevented this exacerbation.
Conclusions:
- Ondansetron effectively reduces behavioral suppression in rodent models during drug treatment and withdrawal.
- Ondansetron does not induce rebound behavioral suppression after withdrawal.
- Ondansetron is a potent inhibitor of withdrawal-induced behavioral suppression from ethanol, nicotine, and cocaine.