Analysis of Ethanol Reinforcement in 1-Day-Old Rats: Assessment Through a Brief and Novel Operant Procedure

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2008-04, Vol.32 (4), p.580-592
• Main Authors: Bordner, Kelly A., Molina, Juan Carlos, Spear, Norman E.
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - psychology; Alcoholism and acute alcohol poisoning; Animals; Animals, Newborn; Biological and medical sciences; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Ethanol; Ethanol - administration & dosage; Female; Male; Medical sciences; Newborn Rat; Ontogeny; Operant Conditioning; Pregnancy; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Reaction Time - physiology; Reinforcement; Reinforcement (Psychology); Time Factors; Toxicology
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.2007.00609.x

Background:  An accumulating body of experimental evidence supports the notion that, early in development, heterogeneous rats exhibit heightened affinity for ethanol ingestion and are sensitive to the drug’s postabsorptive reinforcing effects. The brevity of this ontogenetic period and the limited behavioral repertoire of the newborn represent obstacles in the examination of these phenomena. In the present study, we developed a novel operant technique aimed at examining the neonatal predisposition to gain access to intraoral infusions of different ethanol solutions and other potential reinforcers. Methods:  In all experiments, 1‐day‐old rats were placed in a supine position that allowed access to a touch‐sensitive sensor. In Paired pups, reinforcers were delivered through an intraoral cannula in a fixed‐ratio‐1 schedule, based on their physical contact with the sensor. Yoked controls were included to account for overall magnitude of behavioral responding and were given infusions in accord with behavior of the corresponding Paired pup. The reinforcement effect of milk, water and different ethanol solutions (0.75 to 10% v/v) was assessed using a single 15‐minute conditioning session. Additional pharmacokinetic studies were conducted to determine blood ethanol concentrations attained during the course of the training session. Results:  Within‐subjects analysis revealed that Paired pups rapidly learned to increase the probability of behavioral execution to gain access to a biological reinforcer such as milk (Experiment 1). Follow‐up experiments indicated that relatively low ethanol concentrations are equally likely to support operant performance (Experiments 2a and 3a). It was also observed that Paired pups exhibited surprisingly high levels of responding during an extinction session, particularly when initially trained with milk or 3% v/v ethanol as reinforcers (Experiment 4). The pharmacokinetic studies indicated that, within a short period of time, ethanol was detectable in blood. Levels attained during conditioning varied as a function of the ethanol concentration utilized as a reinforcer (Experiments 2b and 3b). Conclusions:  The present technique appears to represent a valuable tool for examining ethanol self‐administration and seeking behavior of the drug during early ontogeny. The results indicate that newborn rats, subjected to the explicit contingency comprising suckling‐related behaviors and intraoral ethanol delivery (Paired pups), rapidly learn to