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

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, and kappa, opioid receptors in mediating the hyperphagic effects of glucoprivation. (C) 1998 Elsevier Science B.V. All rights reserved.