Naloxone attenuation of ethanol-reinforced operant responding in infant rats in a re-exposure paradigm

Abstract

Rationale: Early ethanol exposure promotes ethanol reinforcement, mediated perhaps by ethanol’s motivational effects. The opioid system mediates ethanol reinforcement, at least in part. Objectives: Modulation of consummatory and seeking behaviors by the opioid system was tested in terms of ethanol or sucrose operant self-administration. Methods: Wistar-derived infant rats were tested in an operant conditioning task. (1) Infants were trained on postnatal days (PDs) 14–17 to obtain 5% sucrose and 3.75% ethanol or water, and evaluated in an extinction session at PD 18. (2) Ethanol (3.75%) was used as reinforcer. At PDs 16–17, 6 h before operant task, pups were re-exposed to ethanol after naloxone injection (0 or 1 mg/kg). (3) Sucrose (5%) acted as reinforcer. Pups were re-exposed to sucrose after naloxone injection. (4) A PD 18 re-exposure trial in which pups were injected with naloxone and re-exposed to ethanol was added. Result: Sucrose and ethanol promoted higher levels of operant responding than water during training and extinction. Re-exposure to ethanol preceded by naloxone decreased nose-poking. A similar profile was observed towards sucrose. No seeking behavior was observed in pups re-exposed to ethanol following naloxone injection during PDs 16–18. Conclusions: Self-administration of ethanol was established in terms of operant responding in preweanling rats with no previous exposure to the drug. Pairing of naloxone with ethanol, at a point separate in time from operant responding, reduced ethanol reinforcement. This indicated participation of the opioid system in ethanol reinforcement. This effect seems not to be unique to ethanol but also is observable when sucrose acts as reinforcer.