Dynorphin A (2-17) attenuates the unconditioned but not the conditioned effects of opiate withdrawal in the rat.
OBJECTIVE
An unbiased place preference conditioning procedure was used to examine the influence of the non-opioid peptide, dynorphin A 2-17 (DYN 2-17), upon the conditioned and unconditioned effects of opiate withdrawal in the rat.


METHODS
Rats were implanted SC with two pellets containing 75 mg morphine or placebo. Single-trial place conditioning sessions with saline and the opioid receptor antagonist naloxone (0.1-1.0 mg/kg; SC) commenced 4 days later. Ten minutes before SC injections, animals received an IV infusion of saline or DYN 2-17 (0.1-5.0 mg/kg). Additional groups of placebo- and morphine-pelleted animals were conditioned with saline and DYN 2-17. During each 30-min conditioning session, somatic signs of withdrawal were quantified. Tests of place conditioning were conducted in pelleted animals 24 h later.


RESULTS
Naloxone produced wet-dog shakes, body weight loss, ptosis and diarrhea in morphine-pelleted animals. Morphine-pelleted animals also exhibited significant aversions for an environment previously associated with the administration of naloxone. These effects were not observed in placebo-pelleted animals. DYN 2-17 pretreatment resulted in a dose-related attenuation of somatic withdrawal signs. However, conditioned place aversions were still observed in morphine-pelleted animals that had received DYN 2-17 in combination with naloxone. Furthermore, the magnitude of this effect did not differ from control animals.


CONCLUSIONS
These data demonstrate that the administration of DYN 2-17 attenuates the somatic, but not the conditioned aversive effects of antagonist-precipitated withdrawal from morphine in the rat. Differential effects of this peptide in modulating the conditioned and unconditioned effects of opiate withdrawal are suggested.
Shippenberg
T S
TS
Integrative Neuroscience Unit, Behavioral Pharmacology Branch, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. TShippen@intra.nida.nih.gov
Funada
M
M
Schutz
C G
CG
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004399:Dynorphins / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D010446:Peptide Fragments; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; D004399:Dynorphins; C082245:dynorphin (2-17)