Abstract
Anatomical evidence indicates that cholinergic and opioidergic systems are co-localized and acting on the same neuron. However, the regulatory mechanisms between cholinergic and opioidergic system have not been well characterized. In the present study, the potential involvement of μ-opioid receptors in mediating the changes of toxic signs and muscarinic receptor binding after administration of irreversible anti-acetylcholinesterase diisopropylfluorophosphate (DFP) was investigated. DFP (1 mg/kg/day, subcutaneous injection, s.c.)-induced tremors and chewing movements were monitored during the 28-day treatment period in μ-opioid receptor knockout and wild type mice. Autoradiographic studies of total, M1, and M2 muscarinic receptors were conducted using [3H]-quinuclidinyl benzilate, [ 3H]-pirenzepine, and [3H]-AF-DX384 as ligands, respectively. DFP-induced tremors in both μ-opioid receptor knockout and wild type mice showed tolerance development. However, DFP-induced tremors in μ-opioid receptor knockout mice showed delayed tolerance development than that of DFP-treated wild type controls. DFP-induced chewing movements in both μ-opioid receptor knockout and wild type mice failed to show development of tolerance after four weeks of treatment. M2 muscarinic receptor binding of DFP-treated μ-opioid receptor knockout mice was significantly decreased than that of the DFP-treated wild type controls in the striatum, but not in the cortex and hippocampus. However, there were no significant differences in total and M1 muscarinic receptor binding between DFP-treated μ-opioid receptor knockout and wild type mice in the cortex, striatum and hippocampus. These studies indicate that μ-opioid receptors play an important role through the striatal M2 muscarinic receptors to regulate the development of tolerance to DFP-induced tremors.
Original language | English (US) |
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Pages (from-to) | 43-59 |
Number of pages | 17 |
Journal | Journal of Toxicological Sciences |
Volume | 30 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2005 |
Keywords
- Autoradiography
- Diisopropylfluorophosphate
- M1 and M2 muscarinic receptors
- μ-Opioid receptors