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

An unbiased conditioned place preference paradigm was used to evaluate the reward effect of selective endogenous mu-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 microg) induced place preference in a dose-dependent manner; whereas, endomorphin-2 (1-10 microg) 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 mu-opioid receptor antagonist, beta-funaltrexamine. Selective delta-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 kappa-opioid receptor antagonist, WIN 44,441-3. It is concluded that endomorphin-1 produces conditioned place preference, which is mediated by the stimulation of mu-, but not delta- or kappa-opioid receptors, while endomorphin-2 produces conditioned place aversion, which is mediated by the stimulation of mu- and kappa-, but not delta-opioid receptors.