TY - JOUR
T1 - Morphine and morphine-6β-glucuronide-induced feeding are differentially reduced by G-protein α-subunit antisense probes in rats
AU - Silva, Robert M.
AU - Rossi, Grace C.
AU - Mathis, John P.
AU - Standifer, Kelly M.
AU - Pasternak, Gavril W.
AU - Bodnar, Richard J.
N1 - Funding Information:
This research was supported in part by a National Science Foundation Grant (IBN98-16699 to RJB), National Institute of Drug Abuse Grants (DA07274 and DA00220 to GWP and DA00310 to GCR), PSC/CUNY Grant (62307 to RJB) and a CUNY Science Fellowship (RMS).
PY - 2000/9/8
Y1 - 2000/9/8
N2 - Although morphine and its active metabolite, morphine-6β-glucuronide (M6G), each induce μ-opioid receptor-sensitive feeding, different antisense oligodeoxynucleotide (AS ODN) probes directed against the MOR-1 clone produce distinct effects. Thus, MOR-1 AS ODN probes directed against exons 1 or 4 reduce morphine-, but not M6G-induced feeding, whereas probes directed against exons 2 or 3 reduce M6G-, but not morphine-induced feeding. AS ODN probes directed against different G-protein α-subunits differentially reduced morphine (G(iα2)) and M6G (G(iα1))-induced analgesia. The present study evaluated the ability of AS ODN probes directed against G-protein α- subunits to reduce feeding induced by morphine and M6G in rats. The AS ODN probes (25 μg, i.c.v.) were administered once 24 h prior to morphine (5 μg, i.c.v.) or M6G (250 ng) and spontaneous free feeding was assessed 1, 2 and 4 h thereafter. In agreement with analgesic studies, morphine-induced feeding was significantly reduced by the G(iα2) AS ODN probe. Morphine-induced feeding was unaffected by AS ODN probes directed against either G(iα1), G(iα3), G(oα), G(x/zα), G(qα) or a nonsense control probe, and was significantly enhanced by pretreatment with the G(sα) probe. In contrast, M6G-induced feeding was significantly reduced by AS ODN probes directed against either G(iα1), G(iα3) or G(x/zα), whereas AS ODN probes targeting G(iα2), G(oα), G(sα), G(qα) or a nonsense control probe were ineffective. When M6G-induced feeding was assessed at a dose (500 ng) which was sensitive to MOR-1 AS ODN effects, none of the G-protein α-subunit AS ODN probes were effective. These data indicate that morphine and M6G-induced feeding are mediated through different G-protein α-subunits, and provide further evidence for separate and distinct molecular mechanisms mediating these functional responses through different opioid receptors. This strongly suggests that M6G may act through a novel opioid receptor displaying a distinct pharmacological mechanism. (C) 2000 Elsevier Science B.V.
AB - Although morphine and its active metabolite, morphine-6β-glucuronide (M6G), each induce μ-opioid receptor-sensitive feeding, different antisense oligodeoxynucleotide (AS ODN) probes directed against the MOR-1 clone produce distinct effects. Thus, MOR-1 AS ODN probes directed against exons 1 or 4 reduce morphine-, but not M6G-induced feeding, whereas probes directed against exons 2 or 3 reduce M6G-, but not morphine-induced feeding. AS ODN probes directed against different G-protein α-subunits differentially reduced morphine (G(iα2)) and M6G (G(iα1))-induced analgesia. The present study evaluated the ability of AS ODN probes directed against G-protein α- subunits to reduce feeding induced by morphine and M6G in rats. The AS ODN probes (25 μg, i.c.v.) were administered once 24 h prior to morphine (5 μg, i.c.v.) or M6G (250 ng) and spontaneous free feeding was assessed 1, 2 and 4 h thereafter. In agreement with analgesic studies, morphine-induced feeding was significantly reduced by the G(iα2) AS ODN probe. Morphine-induced feeding was unaffected by AS ODN probes directed against either G(iα1), G(iα3), G(oα), G(x/zα), G(qα) or a nonsense control probe, and was significantly enhanced by pretreatment with the G(sα) probe. In contrast, M6G-induced feeding was significantly reduced by AS ODN probes directed against either G(iα1), G(iα3) or G(x/zα), whereas AS ODN probes targeting G(iα2), G(oα), G(sα), G(qα) or a nonsense control probe were ineffective. When M6G-induced feeding was assessed at a dose (500 ng) which was sensitive to MOR-1 AS ODN effects, none of the G-protein α-subunit AS ODN probes were effective. These data indicate that morphine and M6G-induced feeding are mediated through different G-protein α-subunits, and provide further evidence for separate and distinct molecular mechanisms mediating these functional responses through different opioid receptors. This strongly suggests that M6G may act through a novel opioid receptor displaying a distinct pharmacological mechanism. (C) 2000 Elsevier Science B.V.
KW - Antisense oligodeoxynucleotides
KW - Feeding
KW - G-protein α subunits
KW - Morphine
KW - Morphine-6β-glucuronide
UR - http://www.scopus.com/inward/record.url?scp=0034622666&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(00)02621-4
DO - 10.1016/S0006-8993(00)02621-4
M3 - Article
C2 - 10973594
AN - SCOPUS:0034622666
SN - 0006-8993
VL - 876
SP - 62
EP - 75
JO - Brain Research
JF - Brain Research
IS - 1-2
ER -