Differential motivational properties of ethanol during early ontogeny as a function of dose and postadministration time

Abstract

While appetitive reinforcement effects of ethanol are easily detected in rat neonates, such phenomena rarely have been observed in older infants. Recently, Molina et al. [Molina, J. C., Ponce L. F., Truxell, E., & Spear N. E. (2006). Infantile sensitivity to ethanol's motivational effects: ethanol reinforcement during the third postnatal week. Alcohol Clin Exp Res 30, 1506-1519] reported such effects of ethanol in 14-day-olds using a second-order conditioning procedure. Infants also appear to be sensitive to biphasic reinforcement or general motivational effects of ethanol, with appetitive effects seeming to occur early in the state of intoxication and aversive effects predominant during late stages, but tests have been inconclusive. The present study examined the possibility of biphasic motivational effects of ethanol during infancy through the use of second-order conditioning procedures. Preweanling rats (14 days old) experienced intraoral water infusions (conditioned stimulus, CS) either 5-20 or 30-45 min after administration of 0.5 or 2.0 g/kg i.g. ethanol. Pups were then exposed to the CS while over a novel texture (second-order phase). Tests of tactile preference for that texture followed. Locomotive, thermal, hormonal (corticosterone release), and pharmacokinetic patterns likely to underlie the acquisition of ethanol-mediated conditioning were also examined in subsequent experiments. Intraoral CSs paired with either early or late effects of low-dose ethanol (0.5 g/kg, blood ethanol concentration: 40 mg%) became positive second-order reinforcers. Appetitive effects were also exhibited by pups exposed to the CS during commencement of the toxic episode induced by a 2.0 g/kg ethanol dose, 5-20 min after administration of ethanol, whereas aversions emerged when CS presentation occurred 30-45 min postadministration time (blood ethanol concentrations: 157 and 200 mg%, respectively). Overall, the results indicate that infants rapidly detect differential motivational properties of ethanol as a function of dose or drug postadministration time. Relatively neutral stimuli associated with these properties are later capable of acting as either positive or aversive reinforcers. Thermal and motor responses that accompany ethanol intoxication do not seem to be directly associated with differential hedonic properties of the drug at this stage of development.

Figure 1

Time spent over sandpaper and the novel surface as a function of intraoral water paired with early (5-20 min postadministration) or late (30-45 min postadministration) ethanol dose (0.5 or 2.0 g/kg) and time at test (1-5 min). UP groups, that do not exhibit significant differences between them, have been collapsed across drug treatment and postadministration time. In this study, intraoral water was subsequently paired with sandpaper. Vertical lines illustrate standard error of the means.

Figure 2

Rectal temperatures (° C) during postnatal day (PD) 14 and 15 (first- and second-order conditioning phases, respectively) as a function of ethanol dose (0.5, 2.0 or 0.0 g/kg, water) and time point of measurement (PD 14: Baseline and after CS Exposure; PD 15: Baseline and after the first and second CS exposure). To facilitate visualization, data has been collapsed across postadministration time (early or late). This factor failed to significantly affect the pattern of results during both PD 14 and 15 and did not significantly interacted with the remaining factors. Vertical lines illustrate standard error of the means.

Figure 3

Locomotor activity during postnatal days (PD) 14 and 15 as a function of ethanol dose (0.5, 2.0 or 0.0 g/kg, water) and time point of measurement (PD 14: Baseline and First-order conditioning phase; PD 15: Infusion Trial 1 and 2). To facilitate visualization, data has been collapsed across postadministration time (early or late). This factor did not have a significantly effect neither during the habituation and conditionining phases conducted on PD 14 nor on the second-order conditioning phase (PD 15). Also, postadministration time did not significantly interacted with the remaining factors. Vertical lines illustrate standard error of the means.

Figure 4

Blood ethanol concentrations (mg%) as a function of ethanol dose (0.50 or 2.0 g/kg) and postadministration time (12.5 or 37.5 min). Vertical lines illustrate standard errors of the means.