Tetrahydroaminoacridine inhibits high voltage spindle activity in aged rats after acute and chronic treatment.

The present study evaluated the ability of tetrahydroaminoacridine (THA) to reverse the age-related increase in high voltage spindles (HVS). THA was injected either 15 or 90 min before EEG recordings were made. A THA dose of 3 mg/kg IP decreased the incidence of HVS, but was ineffective at doses of 0.03 and 1 mg/kg. The HVS suppressing effect of THA (3 mg/kg) declined during a 10-day treatment period. After 10 days chronic THA treatment, a challenge dose of 6 mg/kg of THA reinstated HVS suppressing effect of THA. Our results suggests that (1) THA reverses the age-related deficit of thalamo-cortical activation (2) tolerance develops to THA-induced HVS suppression (3) anti-cholinesterase activity may be important for the efficacy of THA in decreasing HVS because pilocarpine, a muscarinic agonist, also decreased HVS.