Advertisement

Ondansetron alters human alcohol intoxication

  • Robert M. Swift
    Correspondence
    Address reprint requests to Robert M. Swift, MD, PhD, Roger Williams Medical Center, Department of Psychiatry, 825 Chalkstone Avenue, Providence, RI 02908.
    Affiliations
    Department of Psychiatry and Human Behavior, Brown University Medical School, and the Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA
    Search for articles by this author
  • Dena Davidson
    Affiliations
    Department of Psychiatry and Human Behavior, Brown University Medical School, and the Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA
    Search for articles by this author
  • William Whelihan
    Affiliations
    Department of Psychiatry and Human Behavior, Brown University Medical School, and the Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA
    Search for articles by this author
  • Oleg Kuznetsov
    Affiliations
    Department of Psychiatry and Human Behavior, Brown University Medical School, and the Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      There is considerable evidence that serotonin-3 (5-HT3) receptor antagonists modulate some of the behavioral effects of alcohol, and may decrease alcohol consumption. To better clarify the mechanism of action of 5-HT3 antagonists on these behaviors, we investigated the effects of the 5-HT3 antagonist, ondansetron, on several subjective and objective measures of alcohol intoxication in social drinkers. Twelve nonalcoholic, social drinkers received either 8 mg ondansetron, p.o., or placebo during one of two test sessions in a crossover, double-blind protocol. Both conditions were followed by a standard, intoxicating dose of alcohol. Subjective and objective measures of intoxication including mood, physical sensations, performance changes, and alcohol pharmacokinetics were determined. To control for ondansetron effects, 10 additional subjects received either ondansetron or placebo, followed by a nonintoxicating, “placebo” dose of alcohol during a second crossover double-blind protocol. Ondansetron was found to augment certain stimulant, sedative, and discriminant effects of alcohol, without affecting psychomotor performance or alcohol pharmacokinetics. Ondansetron had minimal effects on subjects receiving placebo alcohol. These data suggest that the reductions in alcohol consumption observed in animals and humans treated with ondansetron may be mediated by increases in subjective intoxication, and/or increases in the aversive effects of alcohol.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Baker EL
        • Letz R
        • Fidler A
        A computer-administered neurobehavioral evaluation system for occupational and environmental epidemiology.
        J Occup Med. 1985; 27: 206-212
        • Barrett JE
        • Gleeson S
        • Grant KA
        • Robertson DW
        Antagonism of the anxiolytic-like effects of ethanol by the 5HT3 antagonists zatosetron and MDL 72222.
        in: Proceedings of the American College of Neuropsychopharmacology Annual Meeting, Nashville, TN1991: 143
        • Benkelfat C
        • Murphy DL
        • Hill JL
        • George DT
        • Nutt D
        • Linnoila M
        Ethanollike properties of serotonergic partial anagonst m-chlorophenylpiperazine in chronic alcoholic patients.
        Arch Gen Psychiatry. 1991; 48: 383
        • Carboni E
        • Acquas E
        • Frau R
        • DiChiara G
        Differential inhibitory effects of a 5HT3 antagonist on drug-induced stimulation of dopamine release.
        Eur J Pharmacol. 1989; 164: 515-519
        • Costall B
        • Jones BL
        • Kelly ME
        • et al.
        Ondansetron inhibits a behavioral consequence of withdrawing from drugs of abuse.
        Pharmacol Biochem Behav. 1990; 36: 339-344
        • Doty P
        • Zacny J
        • deWit H
        The effects of ondansetron pretreatment on acute responses to ethanol in social drinkers.
        Beh Pharm. 1994; 5: 461-469
        • deWit H
        • Griffiths RR
        Testing the abuse liability of anxiolytic and hypnotic drugs in humans.
        Drug Alcohol Dependence. 1991; 28: 83-111
        • deWit H
        • Uhlenhuth E
        • Pierri J
        • Johanson C
        Individual differences in behavioral and subjective responses to ethanol.
        in: Pohorecky L Brick J Stress and Ethanol Use. Elsevier Biomedical, Washington DC1987: 153-169
        • Dyr W
        • McBride WJ
        • Murphy JM
        • Lumeng L
        • Li T-K
        Multiple injections of 5HT3 antagonists reduce alcohol consumption of the P line of rats.
        Alcoholism Clin Exp Res. 1993; 16: 261-265
        • Gorelick DA
        • Paredes A
        Effect of fluoxetine on alcohol consumption in male alcoholics.
        Alcoholism Clin Exp Res. 1992; 16: 261-265
        • Grant KA
        • Barrett JE
        Blockade of the discriminative stimulus effects of ethanol with 5HT3 receptor antagonists.
        Psychopharmacology. 1991; 104: 451-456
        • Hodge CW
        • Samson HH
        • Lewis RS
        • Erickson HL
        Specific decreases in ethanol but not water-reinforced responding produced by the 5-HT antagonist ICS 205-930.
        Alcohol. 1993; 10: 191-196
        • Hoyer D
        Serotonin 5-HT3, 5-HT4, and 5HT-M receptors.
        Neuropsychopharmacology. 1990; 3: 371-383
        • Johnson BA
        • Campling GM
        • Griffiths P
        • Cowen PJ
        Attenuation of some ethanol-induced mood changes and the desire to drink by 5HT3 receptor blockade: A preliminary study in healthy male volunteers.
        Psychopharmacology. 1993; 112: 142-144
        • Knapp DJ
        • Pohorecky LA
        Zacopride, a 5HT3 receptor antagonist reduces voluntary ethanol consumption in rats.
        Pharmacol Biochem Behav. 1992; 41: 847-850
        • Kranzler HR
        • Anton RF
        Implications of recent neuropsychopharmacologic research for understanding the etiology and development of alcoholism.
        J Consult Clin Psychiatry. 1994; 62: 1116-1126
        • Kranzler HR
        • Meyer RE
        An open trial of buspirone in alcoholics.
        J Clin Psychopharmacol. 1989; 9: 379-380
        • LeMarquond D
        • Pihl RO
        • Benkelfat C
        Serotonin and ethanol intake, abuse and dependence: Findings of animal studies.
        Biol Psychiatry. 1994; 36: 394-421
        • Linnoila M
        • Eckardt M
        • Durcan M
        • et al.
        Interactions of serotonin with ethanol: Clinical and animal studies.
        Psychopharmacol Bull. 1987; 23: 452-457
        • Littleton J
        • Little H
        Current concepts of ethanol dependence.
        Addiction. 1994; 89: 1397-1412
        • Maisto S
        • Connors G
        • Tucker H
        • McCollam H
        • Adesso V
        Validation of the sensation scale, a measure of subjective psychobiological responses to ethanol.
        Behav Res Ther. 1980; 18: 37-41
        • Marlin CS
        • Earleywine M
        • Musty RE
        • Perrine MW
        • Swift RM
        Development and validation of the biphasic ethanol effects scale.
        Alcoholism Clin Exp Res. 1993; 17: 140-146
        • Nagoshi C
        • Wilson J
        • Plomin R
        Use of regression residuals to quantify individual differences in acute sensitivity and tolerance to ethanol.
        Alcoholism Clin Exp Res. 1986; 10: 343-349
        • Naranjo CA
        • Bremner KE
        Serotonin-altering medications and desire, consumption and effects of alcohol—treatment implications.
        EXS. 1994; 71: 209-219
        • Naranjo CA
        • Sellers EM
        • Roach CA
        • et al.
        Zimelidine-induced variations in ethanol intake by non-depressed heavy drinkers.
        Clin Pharmacol Ther. 1984; 35: 374-381
        • Naranjo CA
        • Sellers EM
        • Lawrin MO
        Modulation of ethanol intake by serotonin uptake inhibitors.
        J Clin Psychiatry. 1986; 47 (suppl): 16-22
        • Naranjo CA
        • Sellers EO
        • Sullivan JT
        • et al.
        The serotonin uptake inhibitor citalopram attenuates ethanol intake.
        Clin Pharmacol Ther. 1987; 41: 266-274
        • Sellers EM
        • Higgins GA
        • Tomkins DM
        Serotonin receptor subtypes and ethanol consumption.
        in: Proceedings of the American College of Neuropsychopharmacology Annual Meeting. 1991: 84
        • Soubrie P
        Reconciling the role of central serotonin in human and animal behavior.
        Behav Brain Sci. 1986; 9: 319-364
        • Sullivan JT
        • et al.
        Ondansetron decreases cocaine intoxication.
        in: Problems of Drug Dependence. NIDA Res Mono, New York1991
        • Swift RM
        • Whelihan W
        • Kuznetsov O
        • Buongiorno G
        • Hsuing H
        Naltexone-induced alterations in human ethanol intoxication.
        Am J Psychiatry. 1994; 151: 1463-1467
        • Tollefson GD
        • Lancaster SP
        • Montague-Clouse J
        The association of buspirone and its metabolite 1-pyrimidinylpiperazine in the remission of comorbid anxiety with depressive features and alcohol dependence.
        Psychopharmacol Bull. 1991; 27: 163-170
        • Toneatto T
        • Romach MK
        • Sobell MK
        • et al.
        Ondansetron, a 5HT3 antagonist reduces ethanol consumption in ethanol abusers.
        Alcoholism Clin Exp Res. 1991; 15: 382
        • Watson PE
        Total body water and blood alcohol levels: Updating the fundamentals.
        in: Crow KE Batt RD Human Metabolism of Alcohol. vol 1. CRC, Washington, DC1989: 41-56
        • Wilson J
        • Nagoshi C
        Adult children of alcoholics: Cognitive and psychomotor characteristics.
        Br J Addiction. 1988; 83: 809-820
        • Wise R
        • Bozarth M
        A psychomotor stimulant theory of addiction.
        Psychol Rev. 1987; 94: 469-492
        • Wozniak KM
        • Pert A
        • Linnoila M
        Anatagonism of 5-HT3 receptors attenuates the effect of ethanol on extracellular dopamine.
        Eur J Pharmacol. 1990; 187: 287-289