Lack of reward and locomotor stimulation induced by heroin in mu-opioid receptor-deficient mice.
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.
Contarino
Angelo
A
Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA. angelo.contarino@unipd.it
Picetti
Roberto
R
Matthes
Hans W
HW
Koob
George F
GF
Kieffer
Brigitte L
BL
Gold
Lisa H
LH
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology*; D003932:Heroin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012201:Reward
D006213:Hallucinogens; D017450:Receptors, Opioid, mu; D003932:Heroin; D003042:Cocaine