Modification of place preference conditioning in mice by systemically administered [Leu]enkephalin.

[Leu]enkephalin (300 micrograms/kg, i.p.) induced either a positive or negative conditioned place preference response in mice depending on whether the animals were trained against or towards their initial preference. Induction of a positive preference (300 micrograms/kg) was partially blocked by simultaneous addition of methylnaloxonium (10 mg/kg, i.p.), an opioid antagonist that does not readily cross the blood-brain barrier; methylnaloxonium alone (3 or 10 mg/kg) had no effect on the place preference response. The results indicate that [Leu]enkephalin treatment reverses the initial preference of the animal regardless of training, and that some aspect of the [Leu]enkephalin effect on place preference conditioning is mediated by peripheral opioid receptors. These findings challenge the notion that place preference conditioning is a simple measure of opioid reward.