Objective: To monitor pre and postsynaptic receptor responsiveness and consumption of ethanol following the repeated administration of a selective serotonin-1A receptor agonist, 8-hydroxy-2-di-n-propylaminotetralin (8-OH-DPAT), to ethanol treated rats.
Design: The experimental protocol was designed to administer ethanol orally to rats for three weeks and 8-OH-DPAT during the 3rd week.
Place and duration of study: The experiments were performed in the department of Biochemistry, Karachi University. Samples collected after three weeks of treatment were analyzed within a week.
Subjects and methods: The study was conducted on 24 males albino Wistar rats treated with ethanol for three weeks. 8-OH-DPAT at a dose of 1mg/kg or saline was injected to ethanol treated rats from day 1 to day 5 during the 3rd week to monitor the effects on ethanol consumption. Pre and postsynaptic responses to 8-OH-DPAT were monitored by injecting the drug on the 6th day to a group of 5-day saline and a group of 5-day 8-OH-DPAT injected animals. Control animals of the two groups were injected with saline.
Results: Before the injection of 8-OH-DPAT, weekly intakes of ethanol were highly comparable in the two groups. Administration of 8-OH-DPAT, from day 1 to day 5, decreased ethanol intake. Pre and postsynaptic serotonin-1A receptor dependent responses monitored on the 6th day were higher in 5-day saline than 5-day 8-OH-DPAT injected animals.
Conclusion: A decrease in the effectiveness of negative feedback control over the synaptic availability of serotonin following 5-day administration of 8-OH-DPAT is involved in the decreases of ethanol consumption.