RT Journal Article
SR Electronic
T1 Early Postnatal Stress Alters Place Conditioning to Both μ- and κ-Opioid Agonists
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 313
OP 318
DO 10.1124/jpet.107.129908
VO 325
IS 1
A1 Clifford C. Michaels
A1 Stephen G. Holtzman
YR 2008
UL http://jpet.aspetjournals.org/content/325/1/313.abstract
AB 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 κ-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 κ-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 κ-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 κ-opioid agonists when measured using place conditioning. The American Society for Pharmacology and Experimental Therapeutics