Antisense mapping of opioid receptor clones : effects upon 2-deoxy-D-glucose-induced hyperphagia

Abstract Antisense oligodeoxynucleotides (AS ODNs) directed against exons 1 and 2 of the MOR-1 clone significantly and markedly reduced (81–93%) hyperphagia induced by the anti-metabolic glucose analogue, 2-deoxy- d -glucose (2DG) across a 4 h time course. AS ODNs directed against exons 3 or 4 of the MOR-1 clone had a more limited (1–2 h) duration of action upon 2DG-induced hyperphagia. 2DG-induced hyperphagia was significantly reduced by AS ODNs directed against exon 2 (44–51%), but not exons 1 or 3 of the KOR-1 clone across a 4 h time course. Whereas an AS ODN probe directed against the KOR3/ORL-1 clone produced small (36%), but significant reductions in 2DG-induced hyperphagia, an AS ODN probe directed against the DOR-1 clone was ineffective. These data provide further converging evidence for the roles of primarily mu, but also kappa 1 and kappa 3 opioid receptors in mediating the hyperphagic effects of glucoprivation.