SELECTIVE MUSCARINIC ANTAGONISTS DIFFERENTIALLY AFFECT IN-VIVO ACETYLCHOLINE-RELEASE AND MEMORY PERFORMANCES OF YOUNG AND AGED RATS

Brain acetylcholine release and memory performance were investigated i n young (three- to six-months) and old (20- to 24-months) rats. Acetyl choline release was measured in vivo in the cortex and hippocampus of freely-moving animals, under basal conditions and in the presence of t he following muscarinic antagonists: scopolamine, (+/-)-5,11-dihydro-1 1-[[(2-[2-[(dipropylamino) methyl]-1-piperidinyl] ethyl) amino] rbonyl ]-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one (AFDX 384) and pirenzepin e. The amount of acetylcholine released from the cortex and hippocampu s of old rats was significantly reduced. In the presence of scopolamin e and AFDX 384 but not of pirenzepine, the acetylcholine release was s ignificantly higher in the old than the young rats, suggesting that ch anges in presynaptic M2/M4 muscarinic receptor function occur with agi ng in the two brain regions. Cognitive capacities were evaluated using two different behavioural tasks: object recognition and passive avoid ance response. Old rats were unable to discriminate between familiar a nd novel objects and had impaired performance in the passive avoidance test. AFDX 384 restored the performance in both tests. Furthermore, i n young rats AFDX 384 reversed the impairment of both object recogniti on and passive avoidance response induced by scopolamine. The effect o f AFDX 384 on acetylcholine release and behaviour in the old rats offe rs further support to a relationship between the age-related cholinerg ic hypofunction and cognitive impairment and indicates the blockade of presynaptic muscarinic receptors as a possible selective target for t herapeutic strategies aimed at improving age-associated memory deficit s. (C) 1997 IBRO. Published by Elsevier Science Ltd.