Lack of reward and locomotor stimulation induced by heroin in mu-opioid receptor-deficient mice.
Contarino, Angelo;
Picetti, Roberto;
Matthes, Hans W;
Koob, George F;
Kieffer, Brigitte L;
Gold, Lisa H;
(2002)
Lack of reward and locomotor stimulation induced by heroin in mu-opioid receptor-deficient mice.
European journal of pharmacology, 446 (1-3).
pp. 103-109.
ISSN 0014-2999
DOI: https://doi.org/10.1016/s0014-2999(02)01812-5
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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.
