A 3-day exposure to 10% ethanol with 10% sucrose successfully initiates ethanol self-administration

Abstract

The initiation phase of ethanol self-administration is difficult to study using the well-established, sucrose-fading procedure due to the changing concentrations of ethanol in the first few days. The purpose of this experiment was to test whether a modified sucrose-substitution procedure in which rats are initially exposed to high concentrations of ethanol and sucrose for three days would successfully initiate ethanol self-administration. Male Long-Evans rats were trained to lever-press with a 10% sucrose solution in which four or 20 responses allowed 20-min access to the solution. Subsequently, rats were exposed to a 3-day period of operant self-administration of 10% sucrose+10% ethanol. This constant-concentration exposure was followed by the standard procedure in which sucrose is completely faded out. The establishment of ethanol self-administration was determined by ethanol intake, pre- and postprocedure two-bottle choice preference tests, and extinction trials. The mean ethanol intake was 2.2 times higher on day 2 compared with day 1 on the 10% sucrose+10% ethanol solution. After fading out the sucrose, the daily intake of 10% ethanol solution over 5 days was stable at approximately 0.57 g/kg. Ethanol preference was approximately threefold higher after the modified sucrose-fading procedure. Responding during a single session extinction test was dramatically increased from 4 to 61+/-13 or 20 to 112+/-22 responses in 20 min. Similar to the standard sucrose-fading method, we did not observe a significant relationship between extinction responding and ethanol intake. Blood alcohol concentrations were 4.5 mM 20 min after consumption began. We conclude that initiation and establishment of ethanol self-administration will occur using this modified sucrose-fading procedure.

Fig. 1

Ethanol intake during first three days of operant self-administration of 10% sucrose and 10% ethanol and last five days of 10% ethanol. Ethanol intakes (g/kg) are presented as mean ± SEM (n=32). * indicates a statistically significant difference in ethanol intake compared with day 1 (p < .05).

Fig. 2

Ethanol intake (licks) during the various stages of the protocol. The licks represent the ethanol consumption during the operant self-administration of the last day of 10% sucrose, the first three days of 10% sucrose and 10% ethanol, the two days of 5% sucrose and 10% ethanol, the two days of 2% sucrose and 10% ethanol, and the last five days of 10% ethanol. Ethanol intakes (licks) are presented as mean ± SEM (n=19–22). * indicates a statistically significant difference between the indicated groups by post hoc analysis after significance was found for the overall ANOVA.

Fig. 3

Extinction responding versus prior day ethanol intake. Ethanol intake is shown in g/kg for the last day of access to 10% ethanol for rats that had been trained using an RR of 4 (n=14). The line indicates the linear regression which was not statistically significant.