Relationship between the central stimulation of atropine and cholinergic system

The spontaneous activity of mice increased after atropine 5 mg/kg ip, and decreased when atropine was combined with hemicholine 0.2 mg/kg icv, physostigmine 0.5 mg/kg ip, diazepam 10 mg/kg ip or phenobarbital 100 mg/kg ip, repectively. The activity of mice was increased when atropine was combined with 4-aminophyridine 5 mg/kg ip. In rabbits, 5-10 min after icv atropine 1 mg/kg, paroxysmal convulsions and tonic spasm were seen. EEG revealed low voltage and rapid waves,seizure high voltage spinal waves( 1-2 c/s and 10-20 c/s) and 70% rabbits died. If hemicholine 100 microg/kg icv was given 24 h beforehand or scopolaming 3 mg/kg icv was used together with atropine, central stimulation became less intense,but 4-aminopyridine 1 microg/kg icv increased it effect. Physostigmine 0.3 mg/kg iv,contrast to that in mice ,did not alter the central stimulation of rabbits, but diazepam 2 mg/kg iv and Phenobarbital 60 mg/kg iv antagonized atropine very well.These results suggest that the central excitatory effect of atropine may be attributed to the blockage of inhibitory muscarinic receptors and enhancement of Ach releasing in brain.