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BEHAVIORAL PHARMACOLOGY

Early Postnatal Stress Alters Place Conditioning to Both µ- and -Opioid Agonists

Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia

Clinical literature has established a link between early childhood incidents of neglect and trauma and adult problems with substance abuse. In rats, such early life stress has been modeled using a maternal separation (MS) paradigm in which rat pups were removed from their mothers for a few hours daily during the first two postnatal weeks. In this study, we used the MS model to investigate the effects of early postnatal stress on place conditioning to both µ- and -opioid agonists in male and female Long-Evans rats. Offspring of both rearing conditions [MS or nonhandled (NH)] were conditioned using a biased procedure to saline, the µ-opioid agonist morphine (3.0, 5.6, and 10 mg/kg s.c.), or the -opioid agonist spiradoline (0.3, 1.0, and 3.0 mg/kg) for 3 days, followed by a drug-free place-conditioning test 24 h later. Saline was administered in the morning, 30 min before confinement in one compartment, whereas morphine or spiradoline was administered in a similar manner 6 h later in the opposite compartment. MS offspring spent significantly more time in the morphine-paired compartment than NH offspring, indicating a greater place preference for the µ-opioid agonist. In the case of spiradoline, NH offspring spent significantly less time in the spiradoline-paired compartment, indicating a greater aversion to the -opioid agonist in these animals than in MS offspring. These findings indicate that early postnatal stress can significantly alter the rewarding or aversive value of µ- and -opioid agonists when measured using place conditioning.

Address correspondence to: Dr. Clifford C. Michaels, Emory University, Department of Pharmacology, 1510 Clifton Road, Suite 5074, Atlanta, GA 30322. E-mail: ccmicha{at}emory.edu