Dynorphin A (2-17) attenuates the unconditioned but not the conditioned effects of opiate withdrawal in the rat

Objectives: 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.