Anatomical evidence indicates that cholinergic and opioidergic systems are co-localized and acting on the same neurons. However, the regulatory mechanisms between cholinergic and opioidergic system have not been well characterized. In the present study, we investigated whether there are compensatory changes of acetylcholinesterase activity and cholinergic receptors in mice lacking μ-opioid receptor gene. The acetylcholinesterase activity was determined by histochemistry assay. The cholinergic receptor binding was carried out by quantitative autoradiography using [3H]-quinuclidinyl benzilate (nonselective muscarinic receptors), N-[3H]-methylscopolamine (nonselective muscarinic receptors), [3H]-pirenzepine (M1 subtype muscarinic receptors) and [3H]-AF-DX384 (M2 subtype muscarinic receptors) in brain slices of wild-type and μ-opioid receptor knockout mice. The acetylcholinesterase activity of μ-opioid receptor knockout mice was higher than that of the wild-type in the striatal caudate putamen and nucleus accumbens, but not in the cortex and hippocampus areas. In addition, the bindings in N-[3H]-methylscopolamine and [3H]-AF-DX384 of μ-opioid receptor knockout mice were significantly lower when compared with that of the wild-type controls in the striatal caudate putamen and nucleus accumbens. However, there were no significant differences in bindings of [ 3H]-quinuclidinyl benzilate and [3H]-pirenzepine between μ-opioid receptor knockout and wild-type mice in the cortex, striatum and hippocampus. These data indicate that there are up-regulation of acetylcholinesterase activity and compensatory down-regulation of M2 muscarinic receptors in the striatal caudate putamen and nucleus accumbens of μ-opioid receptor knockout mice.
Bibliographical noteFunding Information:
The authors wish to thank Dr. Susan E. Wellman for her generous help in Cyclone Storage Phosphor System. The project described was partially supported by research funds from the Grant R06/CCR419466 (to IKH), the Human Science Grant Foundation of Japan (to IKH), and the Center of Psychiatric Neuroscience at the UMC which is supported by NIH Grant RRl7701 (to TM).
- Acetylcholine receptors: muscarinic
- M1 and M2 muscarinic receptors
- Mu-opioid receptor knockout mice
- Neurotransmitters, modulators, transporters, and receptors