Serotonin receptor antagonism of alcohol intake: Effects of drinking conditions

D. L. McKinzie, R. Eha, R. Cox, R. B. Stewart, W. Dyr, J. M. Murphy, W. J. McBride, L. Lumeng, T. K. Li

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)291-298
Number of pages8
JournalAlcohol
Volume15
Issue number4
DOIs
StatePublished - May 1998

Fingerprint

antagonism
Serotonin Receptors
Drinking
Ethanol
alcohol
Alcohols
Serotonin 5-HT3 Receptor Antagonists
Rats
tropisetron
Group
paradigm
food
water
Receptors, Serotonin, 5-HT3
Saccharin
Injections
Level control
Values
Appointments and Schedules
Food

Keywords

  • 5-HT antagonists
  • Alcohol drinking conditions
  • Alcohol-preferring rats
  • ICS 205-930
  • MDL 72222

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Neuroscience(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

McKinzie, D. L., Eha, R., Cox, R., Stewart, R. B., Dyr, W., Murphy, J. M., ... Li, T. K. (1998). Serotonin receptor antagonism of alcohol intake: Effects of drinking conditions. Alcohol, 15(4), 291-298. https://doi.org/10.1016/S0741-8329(97)00132-8

Serotonin receptor antagonism of alcohol intake : Effects of drinking conditions. / McKinzie, D. L.; Eha, R.; Cox, R.; Stewart, R. B.; Dyr, W.; Murphy, J. M.; McBride, W. J.; Lumeng, L.; Li, T. K.

In: Alcohol, Vol. 15, No. 4, 05.1998, p. 291-298.

Research output: Contribution to journalArticle

McKinzie, DL, Eha, R, Cox, R, Stewart, RB, Dyr, W, Murphy, JM, McBride, WJ, Lumeng, L & Li, TK 1998, 'Serotonin receptor antagonism of alcohol intake: Effects of drinking conditions', Alcohol, vol. 15, no. 4, pp. 291-298. https://doi.org/10.1016/S0741-8329(97)00132-8
McKinzie DL, Eha R, Cox R, Stewart RB, Dyr W, Murphy JM et al. Serotonin receptor antagonism of alcohol intake: Effects of drinking conditions. Alcohol. 1998 May;15(4):291-298. https://doi.org/10.1016/S0741-8329(97)00132-8
McKinzie, D. L. ; Eha, R. ; Cox, R. ; Stewart, R. B. ; Dyr, W. ; Murphy, J. M. ; McBride, W. J. ; Lumeng, L. ; Li, T. K. / Serotonin receptor antagonism of alcohol intake : Effects of drinking conditions. In: Alcohol. 1998 ; Vol. 15, No. 4. pp. 291-298.
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abstract = "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.",
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