Opposite conditioned place preference responses to endomorphin-1 and endomorphin-2 in the mouse

  • Wu H
  • MacDougall R
  • Clithero A
 et al. 
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Abstract

An unbiased conditioned place preference paradigm was used to evaluate the reward effect of selective endogenous μ-opioid ligands, endomorphin-1 and endomorphin-2, in male CD-1 mice. Pre- and post-conditioning free-movement were measured on day 1 and day 5, respectively. Conditioning sessions were conducted twice daily from day 2 through day 4 consisting of the alternate injection of conditioning drug or vehicle. Intracerebroventricular (i.c.v.) injection of endomorphin-1 (0.3-10 μg) induced place preference in a dose-dependent manner; whereas, endomorphin-2 (1-10 μg) dose-dependently induced place aversion. Both endomorphin-1-induced place preference and endomorphin-2-induced place aversion were blocked by pretreatment i.c.v. with μ-opioid receptor antagonist, β-funaltrexamine. Selective δ-opioid receptor antagonist, naltrindole, co-administered i.c.v. with endomorphin-1 or endomorphin-2 did not affect reward effect. However, endomorphin-2-induced place aversion, but not endomorphin-1-induced place preference, was blocked by the i.c.v.-administered selective κ-opioid receptor antagonist, WIN 44,441-3. It is concluded that endomorphin-1 produces conditioned place preference, which is mediated by the stimulation of μ-, but not δ- or κ-opioid receptors, while endomorphin-2 produces conditioned place aversion, which is mediated by the stimulation of μ- and κ-, but not δ-opioid receptors. © 2004 Elsevier Ireland Ltd. All rights reserved.

Author-supplied keywords

  • Brain
  • Conditioned place preference
  • Endomorphins
  • Mouse
  • Opioid
  • Rewarding effect

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Authors

  • Hsiang En Wu

  • Ryan S. MacDougall

  • Andrew D. Clithero

  • Randy J. Leitermann

  • Maia Terashvili

  • Leon F. Tseng

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