The potential involvement of
mu-opioid receptors in mediating the changes of toxic signs and
muscarinic receptor bindings after acute administration of irreversible antiacetylcholinesterase
diisopropylfluorophosphate (
DFP) was investigated.
DFP-induced chewing movement and
tremors were monitored for a period of 180 min in
mu-opioid receptor knockout and wild-type mice. The autoradiographic studies of total, M1, and
M2 muscarinic receptors were conducted using [(3)H]
quinuclidinyl benzilate, [(3)H]
pirenzepine, and [(3)H]AF-DX384 as
ligands, respectively. Saline-treated
mu-opioid receptor knockout and wild-type mice did not show chewing movement or
tremors. Although
DFP (1, 2, or 3 mg/kg,
subcutaneous injection, s.c.)-induced chewing movement and
tremors were shown in a dose-dependent manner, there were no significant differences in
tremors induced by 1 or 2 mg/kg of
DFP between
mu-opioid receptor knockout and wild-type mice. There were also no significant differences in chewing movement induced by all doses of
DFP between
mu-opioid receptor knockout and wild-type mice. However,
DFP (3 mg/kg)-induced
tremors in
mu-opioid receptor knockout mice were significantly increased over those in wild-type controls.
Acetylcholinesterase activity in the striatum of saline-treated
mu-opioid receptor knockout mice was significantly higher than that of the wild-type controls. After administration of
DFP,
acetylcholinesterase activity in the striatum of both
mu-opioid receptor knockout and wild-type mice was significantly decreased (more than 36%, 58%, and 94% reduced at the doses of 1, 2, and 3 mg/kg, respectively) than that of their respective saline controls.
M2 muscarinic receptor binding in saline-treated
mu-opioid receptor knockout mice was significantly lower than that of the wild-type controls in the striatum. However, there were no significant differences in total, M1, or
M2 muscarinic receptor binding in the cortex, striatum, or hippocampus of
mu-opioid receptor knockout and wild-type mice after
DFP administration. Our data show increased
DFP-induced
tremors, compensatory up-regulation of
acetylcholinesterase activity, and compensatory down-regulation of
M2 muscarinic receptors in the striatum of mice lacking
mu-opioid receptor gene. These results suggest that the enhancement of
DFP-induced
tremors may be associated with the compensatory up-regulation of
acetylcholinesterase activity and compensatory down-regulation of
M2 muscarinic receptors in the striatum of
mu-opioid receptor knockout mice.