Retrograde facilitation of verbal memory by trihexyphenidyl in healthy elderly with and without the APOE epsilon4 allele

Abstract

Retrograde facilitation (RF) of information learned prior to acute oral administration of trihexyphenidyl, a preferential muscarinic M1 receptor antagonist which impairs new learning, was studied in 24 healthy elderly subjects. The relationship between the RF induced by this anticholinergic drug and the APOE epsilon4 allele was also examined. Acute adverse performance effects of trihexyphenidyl (1- and 2mg) were determined using the Buschke Selective Reminding Test administered pre-drug and at 1, 2.5, and 5h post-drug. Recall of pre-drug words at the end of the fifth hour neuropsychological assessment (end-of-session recall) was of primary interest. Words studied before drug administration were better recalled following 2mg trihexyphenidyl compared to placebo, and this RF effect was not affected by the APOE epsilon4 allele. Better recall of pre-drug words following 2-mg trihexyphenidyl was associated with a greater amnestic effect of this dose. Our findings demonstrated that RF induced by trihexyphenidyl was related to anterograde amnestic effects of the drug and resulted in part from drug-induced reduction of retroactive interference.