Lack of reward and locomotor stimulation induced by heroin in mu-opioid receptor-deficient mice

Eur J Pharmacol. 2002 Jun 20;446(1-3):103-9. doi: 10.1016/s0014-2999(02)01812-5.


The micro-opioid receptor is the main substrate mediating opiate reward. Multiple micro-opioid receptor subtypes have been postulated to underlie opiate actions. Animals treated with antisense oligonucleotides targeting specific micro-opioid receptor exons show differential sensitivity to morphine versus heroin. The present work examined the rewarding and locomotor activating effects of heroin in mutant mice with a disrupted exon 2 of the micro-opioid receptor. Heroin (1-3 mg/kg) produced significant place preferences and stimulated locomotor activity in wild-type mice, whereas it had no effect in micro-opioid receptor-deficient mice. In contrast, treatment with cocaine (10-30 mg/kg) produced comparable place preferences and locomotor activation in both wild-type and micro-opioid receptor-deficient mice, thus providing evidence that the mutant mice are able to show drug-induced effects in the two behavioral paradigms used here. These results support an essential role for the micro-opioid receptor in the rewarding and locomotor activating effects of heroin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cocaine / pharmacology
  • Conditioning, Psychological / drug effects
  • Female
  • Hallucinogens / pharmacology*
  • Heroin / pharmacology*
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects*
  • Receptors, Opioid, mu / genetics*
  • Reward*


  • Hallucinogens
  • Receptors, Opioid, mu
  • Heroin
  • Cocaine