Morphine induced changes in ethanol-and water-intake are attenuated by the 5-HT3/4 antagonist tropisetron (ICS 205-930)

Psychopharmacology (Berl). 1995 May;119(2):186-92. doi: 10.1007/BF02246160.

Abstract

The opiate agonist morphine has been shown to increase ethanol intake and mesolimbic dopamine (DA) levels. Conversely, the 5-HT3/4 antagonist tropisetron has been shown to decrease ethanol intake and morphine-induced increases in mesolimbic DA levels. This study was designed to test the effects of acutely administered tropisetron on morphine-induced changes in ethanol (6% v/v) and water intake in a two-bottle test procedure. Ten water restricted male rats were injected with combinations of morphine (0.0, 0.56, 1.0, 1.5, 10.0, and 17.0 mg/kg, SC) and tropisetron (0.0, 1.0, 10.0, and 17.0 mg/kg, SC) prior to test sessions. Morphine (1.0 and 1.5 mg/kg) significantly increased absolute (g/kg) and relative ethanol intake (ethanol/total fluid). Tropisetron alone did not affect ethanol or water intake. When tropisetron (10.0 and 17.0 mg/kg) was administered in combination with morphine (1.5 mg/kg), the increase in ethanol intake induced by morphine was attenuated. Tropisetron (1.0 mg/kg) reversed a decrease in ethanol intake induced by morphine (17.0 mg/kg). The two highest doses of tropisetron partially attenuated a significant decrease in water intake produced by morphine (17.0 mg/kg). These data suggest that opiate and 5-HT3 mechanisms could interact in the regulation of ethanol intake. However, the doses of tropisetron tested were high and, therefore, the potential involvement of 5-HT4 receptors or other neurotransmitter systems in regulating ethanol intake is discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcohol Drinking*
  • Animals
  • Dose-Response Relationship, Drug
  • Drinking / drug effects*
  • Drug Synergism
  • Ethanol / administration & dosage*
  • Indoles / pharmacology*
  • Male
  • Morphine / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Self Administration
  • Serotonin Antagonists / pharmacology*
  • Time Factors
  • Tropisetron

Substances

  • Indoles
  • Serotonin Antagonists
  • Ethanol
  • Tropisetron
  • Morphine