Fetal exposure to moderate ethanol doses: heightened operant responsiveness elicited by ethanol-related reinforcers

Abstract

Background: Prenatal exposure to moderate ethanol doses during late gestation modifies postnatal ethanol palatability and ingestion. The use of Pavlovian associative procedures has indicated that these prenatal experiences broaden the range of ethanol doses capable of supporting appetitive conditioning. Recently, a novel operant technique aimed at analyzing neonatal predisposition to gain access to ethanol has been developed. Experiment 1 tested the operant conditioning technique for developing rats described by Arias and colleagues (2007) and Bordner and colleagues (2008). In Experiment 2, we analyzed changes in the disposition to gain access to ethanol as a result of moderate prenatal exposure to the drug.

Methods: In Experiment 1, newborn pups were intraorally cannulated and placed in a supine position that allowed access to a touch-sensitive sensor. Paired pups received an intraoral administration of a given reinforcer (milk or quinine) contingent upon physical contact with the sensor. Yoked controls received similar reinforcers only when Paired pups activated the circuit. In Experiment 2, natural reinforcers (water or milk) as well as ethanol (3% or 6% v/v) or an ethanol-related reinforcer (sucrose compounded with quinine) were tested. In this experiment, pups had been exposed to water or ethanol (1 or 2 g/kg) during gestational days 17 to 20.

Results: Experiment 1 confirmed previous results showing that 1-day-old pups rapidly learn an operant task to gain access to milk, but not to gain access to a bitter tastant. Experiment 2 showed that water and milk were highly reinforcing across prenatal treatments. Furthermore, general activity during training was not affected by prenatal exposure to ethanol. Most importantly, prenatal ethanol exposure facilitated conditioning when the reinforcer was 3% v/v ethanol or a psychophysical equivalent of ethanol's gustatory properties (sucrose-quinine).

Conclusions: The present results suggest that late prenatal experience with ethanol changes the predisposition of the newborn to gain access to ethanol-related stimuli. In conjunction with prior literature, this study emphasizes the fact that intrauterine experience with ethanol not only augments ethanol's palatability and ingestion, but also facilitates the acquisition of response-stimulus associations where the drug acts as an intraoral reinforcer.

FIGURE 1

A: Total number of operant responses (physical contacts with the sensor). B: Maximum level of operant responses in a 30 sec. bin as a function of conditioning treatment (Paired or Yoked) and the solution that was intraorally infused (Milk or Quinine). Vertical lines represent standard errors of the means.

FIGURE 2

Total number of operant responses (physical contacts with the sensor) during acquisition as a function of prenatal treatment, conditioning treatment and solution given as a reinforcer. A) Water and Milk reinforcers. B) Ethanol related solutions [sucrose and quinine (S+Q), 3% or 6% v/v ethanol]. Black bars represent data from Paired pups and white bars show data from Yoked control pups. Vertical lines represent standard errors of the means.

FIGURE 3

Maximum level of operant responses (physical contacts with the sensor) in a given 30 sec bin registered in pups conditioned with ethanol-related reinforcers. Data is depicted as a function of prenatal treatment and conditioning treatment and has been collapsed across the following natural reinforcers (Water and Milk- FIGURE 3A) and across ethanol-related reinforcers (S+Q, 3 % or 6 % of v/v ethanol- FIGURE 3B). Black bars represent data from Paired pups and white bars represent data from Yoked control pups. Vertical lines represent standard errors of the means.

FIGURE 4

Main effects of conditioning treatment during extinction. Data has been collapsed across prenatal treatments and reinforcers. A: Total number of operant responses (physical contacts with the sensor). B: Maximun level of operant responses in a given 30 second bin. C: Latency to display the first operant response. Black bars represent data from Paired pups whereas white bars depict data from Yoked control pups. Vertical lines represent standard errors of the means.