[Intrathecal injection of muscarinic receptors or GDNF antisense oligonucleotides inhibits the increase of c-Fos expression in locus coeruleus of morphine-withdrawal rats].
The antisense approach and immunohistochemistry were used to study the effects of different muscarinic receptor (M) subtypes and glial cell derived neurotrophic factor (GDNF) on the scores of morphine-withdrawal syndrome and the expression of c-Fos in locus coeruleus (LC). Intrathecal injection of M2 receptor antisense oligonucleotides (M2AS-oligo) or GDNF antisense oligonucleotides (GDNFAS-oligo) decreased the scores of morphine withdrawal syndrome. The expression of c-Fos positive neurons in the LC increased in morphine-dependent rats and increased to a greater extent after the injection of naloxone (4mg/kg, ip) in morphine dependent rats. Intrathecal injection of M2AS-oligo or GDNFAS-oligo inhibited the increase of c-Fos expression in LC during morphine withdrawal, but there was no effect in case of M1AS-oligo. The results suggest that M2 receptor of spinal cord mediates the neural activation of LC during morphine withdrawal. And the interaction between neurons and glial cells may be involved in the ascending activation process.
Liu
Hui Fen
HF
Ningbo Institute of Microcirculation & Henbane, Ningbo Aaddiction Research and Treatment Center, Ningbo 315010. lihufen@163.com
Zhou
Wen Hua
WH
Tang
Shuai En
SE
Lai
Miao Jun
MJ
Liu
Sheng
S
Chen
Wei Sheng
WS
Yang
Guo Dong
GD
D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D007150:Immunohistochemistry; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D018727:Muscarinic Antagonists; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D011976:Receptors, Muscarinic; D009020:Morphine