Effects of THA on passive avoidance retention performance of intact, nucleus basalis, frontal cortex and nucleus...

Unilateral quisqualic acid lesions of the nucleus basalis magnocellularis (NBM) produced marked choline acetyltransferase depletion (-67% ipsilateral to lesion) and impaired passive avoidance (PA) retention at 24 hours. Pretraining injections of tacrine (THA: 1, 3 and 5 mg/kg), an anticholinesterase, failed to facilitate PA retention in intact rats. However, the retention performance of NBM-lesioned rats was improved by pretraining administration of THA at 3 mg/kg but not at either 1 or 5 mg/kg. Frontal cortex lesioning did not impair PA retention, and THA at 3 mg/kg had no effect on the PA retention of frontal cortex-lesioned rats. THA at 3 mg/kg failed to improve retention performance of NBM + frontal cortex-lesioned rats. After 10 days of chronic treatment with THA, NBM lesion-induced PA retention deficits were partially restored at both 3- and 5-mg/kg doses. The results suggest that 1) the insult to cholinergic neurons in the NBM may be involved in the PA memory consolidation deficit induced by nonselective quisqualic acid lesioning; 2) the beneficial effects of THA on NBM lesion-induced PA retention deficit occur in a narrow dose range; 3) the alleviating effects of THA on NBM lesion-induced PA memory deficits are blocked by frontal cortex lesions; and 4) the dose-response window for THA-induced PA retention performance improvement is broadened by repeated treatment.