Morphine induced changes in ethanol-and water-intake are attenuated by the 5-HT3/4 antagonist tropisetron (ICS 205-930).
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.
Hodge
C W
CW
Department of Physiology and Pharmacology, Wake Forest University, Bowman Gray School of Medicine, Winston-Salem, N.C. 27157, USA.
Niehus
J S
JS
Samson
H H
HH
D000428:Alcohol Drinking; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D004357:Drug Synergism; D000431:Ethanol / Q000008:administration & dosage*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors; D000077526:Tropisetron
D007211:Indoles; D012702:Serotonin Antagonists; D000431:Ethanol; D000077526:Tropisetron; D009020:Morphine