Abstract
The mu opioid receptor mediates ingestive behavior:mu-selective agonists stimulate food intake and antagonists reduce intake in many ingestive situations. Antisense oligodeoxynucleotides directed against each of the four exons of the MOR-1 clone were equally effective in reducing spontaneous food intake and body weight in rats. However, antisense probes directed against only exon 1 or 4 of the MOR-1 clone reduced mu-mediated analgesia. The present study examined whether central administration of antisense probes directed against each of the four exons of the MOR-1 clone or a missense control altered hyperphagia elicited by themu agonist DAMGO across a range of doses. Antisense probes directed against only exon 1 or 4 blocked hyperphagia at agonist doses of 0.5 and 1.0 μg; this pattern was identical to that observed formu-mediated analgesia. A missense control failed to exert significant effects, which suggests specificity of antisense actions. The effective antisense probes failed to reduce hyperphagia at a higher (5 μg) agonist dose, a result consistent with limitations in down-regulation of receptor proteins by antisense. The muantagonist β-funaltrexamine produced a similar pattern of effects onmu-mediated hyperphagia. The selective actions of antisense probes directed against different exons of the MOR-1 clone in reducing hyperphagia induced by DAMGO suggest that multiple splice variants of the MOR-1 clone exist and raise the possibility of further opioid receptor subclassifications.
Footnotes
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Send reprint requests to: Dr. R. J. Bodnar, Department of Psychology, Queens College, CUNY, 65–30 Kissena Blvd., Flushing, NY 11367.
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↵1 This research was supported in part by NIDA grants DA05746 (L.L.), DA04194 (R.J.B.), DA07274 (G.W.P.), DA00220 (G.W.P.) and DA00310 (G.C.R.) and by a CUNY Project Ascend undergraduate grant (L.B.S.).
- Abbreviations:
- AS ODN
- antisense oligodeoxynucleotide
- βFNA
- β-funaltrexamine
- KOR-1
- kappa opioid receptor clone
- KOR-3
- kappa 3 opioid receptor clone
- MS ODN
- mismatch oligodeoxynucleotide
- M6G
- morphine-6β-glucuronide
- MOR-1
- mu opioid receptor clone
- ORL-1
- orphanin opioid-like receptor clone
- VEH
- vehicle
- DOR-1 = delta opioid receptor clone.
- Received March 11, 1997.
- Accepted May 29, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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