Serotonin3 receptor antagonism of alcohol intake: effects of drinking conditions.
The effects of 5-HT3 receptor antagonists on ethanol intake were examined in the selectively bred alcohol-preferring P line of rats under continuous and limited access to 10% (v/v) ethanol with food and water ad lib. Single daily injections of either MDL 72222 (MDL) or ICS 205-930 (ICS) (0.01-3.0 mg/kg, SC) given 60 min before a 4-h scheduled access period for 4 consecutive days failed at all doses to alter the intake of a 10% (v/v) ethanol solution by P rats. However, multiple daily injections of either MDL (1-3 mg/kg, SC) or ICS (3.0 and 5.0 mg/kg, SC), given three times daily at 4-h intervals, significantly reduced ethanol intake under 24-h free-choice conditions on the first treatment day. Additionally, a single administration of 1.0 mg/kg MDL reduced 24-h free-choice ethanol intake by approximately 50% of control values and had no effect on 24-h saccharin intake. The effects of MDL were further examined in a 2-h schedule access paradigm in which rats received the access period at the same time every day (Fixed) or randomly during the dark cycle (Variable). Although 1.0 mg/kg MDL had little effect on ethanol drinking in the Fixed group, ethanol intake was reduced by 55% of control levels in the Variable group. Overall, the data indicate that drinking conditions influence the effectiveness of 5-HT3 antagonists to reduce ethanol consumption. Furthermore, the results suggest that conditions, associated with limited access ethanol drinking, markedly reduce the actions of 5-HT3 antagonists on ethanol intake.
McKinzie
D L
DL
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis 46202-4887, USA. dmckinzi@iupui.edu
Eha
R
R
Cox
R
R
Stewart
R B
RB
Dyr
W
W
Murphy
J M
JM
McBride
W J
WJ
Lumeng
L
L
Li
T K
TK
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D004326:Drinking / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D012996:Solutions; D014326:Tropanes / Q000008:administration & dosage* / Q000494:pharmacology; D000077526:Tropisetron
D007211:Indoles; D012702:Serotonin Antagonists; D012996:Solutions; D014326:Tropanes; D000077526:Tropisetron; D012439:Saccharin; C042253:bemesetron