Abstract
Rats injected i.p. with AF64A at a dose of 1/3 to 11/25 LD50 showed transient signs of motor disturbance such as ataxia, squatting down and respiratory distress and also longer lasting signs consisting of adipsia, aphagia and loss of body weight. Twenty-four hours after a single injection with AF64A (129 μmol/kg), ACh contents in the cerebral cortex, hippocampus and striatum decreased significantly, and the content in the cerebral cortex still remained at a lowered level even 10 days after injection. When rats received AF64A i.p. with an initial dose of 129 μmol/kg and nine consecutive daily doses of 12.9 μmol/kg and thereafter they were kept with no medication for at least 20 days, the ACh contents in the three brain regions were still significantly reduced. ACh release by electrical stimulation or K+, but not spontaneous release, was significantly reduced in the AF64A treated rats. The T-maze spontaneous alternation behavior in rats treated with AF64A was impaired. The present results indicate that AF64A administered i.p. can induce a long lasting defect in central cholinergic transmission.
