Antisense mapping of the MOR-1 opioid receptor clone: modulation of hyperphagia induced by DAMGO.
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 the mu 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 microg; this pattern was identical to that observed for mu-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 microg) agonist dose, a result consistent with limitations in down-regulation of receptor proteins by antisense. The mu antagonist beta-funaltrexamine produced a similar pattern of effects on mu-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.
Leventhal
L
L
Department of Psychology, Queens College, City University of New York, New York, USA.
Stevens
L B
LB
Rossi
G C
GC
Pasternak
G W
GW
Bodnar
R J
RJ
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology*; D006963:Hyperphagia / Q000139:chemically induced*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*
D004745:Enkephalins; D016376:Oligonucleotides, Antisense; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009271:Naltrexone; C024524:beta-funaltrexamine