Antisense oligodeoxynucleotide to delta opioid receptors attenuates morphine dependence in mice.
The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on the morphine-induced place preference and naloxone-precipitated jumping was examined in morphine-dependent mice. Morphine (5 mg/kg, s.c.) produced a significant place preference. I.c.v. pretreatment with A-oligo (0.01-1 microg/mouse) dose-dependently attenuated this morphine (5 mg/kg, s.c.)-induced place preference, while mismatched oligodeoxynucleotide (M-oligo; 1 microg/mouse, i.c.v.) was ineffective. Naloxone (3 mg/kg, s.c.) precipitated jumping in morphine-dependent mice. I.c.v. pretreatment with A-oligo (1 microg/mouse) attenuated this naloxone (3 mg/kg, s.c.)-precipitated jumping in morphine-dependent mice, while M-oligo (1 microg/mouse, i.c.v.) was ineffective. These data demonstrate that the selective reduction in supraspinal delta opioid receptor function caused by pretreatment with A-oligo attenuated the morphine-induced place preference and naloxone-precipitated jumping in morphine-dependent mice, suggesting that the rewarding effect of and physical dependence on morphine may be modulated by central delta opioid receptors.
Suzuki
T
T
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Ikeda
H
H
Tsuji
M
M
Misawa
M
M
Narita
M
M
Tseng
L F
LF
D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000503:physiopathology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000235:genetics*
D016376:Oligonucleotides, Antisense; D017465:Receptors, Opioid, delta; D009020:Morphine