Evidence for the involvement of presynaptic cholinergic functions in tolerance to XXXX .

@entity1617 @entity1877 @entity3897 @entity972 @entity35 @entity8161 @entity934
@entity35 were treated with @entity8161 ( @entity8161 ) acutely or daily for 14 days. The involvement of various presynaptic and postsynaptic functions of the cholinergic system in the development of tolerance to DFP was studied. Receptor density and affinity of both muscarinic and nicotinic receptors, high-affinity @entity1877 uptake, and [K+]-evoked release of @entity934 ( @entity1617 ) by @entity3897 were not changed after acute administration of 2 mg/kg DFP. Both muscarinic and nicotinic receptors were down-regulated to the same extent (40-50%) after subacute administration of DFP (1 mg/kg) without changes in their affinities. Binding sites of muscarinic receptors were maximally decreased after 7 days of DFP administration. Thereafter, they remained constant throughout 14 days of administration. One hour after the last injection of 2 mg/kg DFP to subacutely treated @entity35 , the maximum velocity of high-affinity @entity1877 uptake was significantly decreased in the striatum (33%) and hippocampus (53%) without changes in Km values. Twenty-four hours after the last injection of DFP, only a higher dose of DFP (2 mg/kg) significantly inhibited @entity1877 uptake. @entity972 -evoked release of @entity1617 by slices of striatum was not different between acutely and subacutely treated @entity35 . However, the release of @entity1617 by slices of striatum and hippocampus was significantly increased by @entity3897 in subacutely treated @entity35 . It is suggested that along with the down-regulation of the postsynaptic receptors, subsensitivity of presynaptic functions of the cholinergic synapse also develops during subacute administration of DFP.
