HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Selective muscarinic antagonists differentially affect in vivo acetylcholine release and memory performances of young and aged rats.

Abstract
Brain acetylcholine release and memory performance were investigated in young (three- to six-months) and old (20- to 24-months) rats. Acetylcholine release was measured in vivo in the cortex and hippocampus of freely-moving animals, under basal conditions and in the presence of the following muscarinic antagonists: scopolamine, (+/-)-5,11-dihydro-11-[[(2-[2-[(dipropylamino) methyl]-1-piperidinyl]ethyl) amino] carbonyl]-6H-pyrido(2,3-b)(1,4)-benzodiazepine-6-one (AFDX 384) and pirenzepine. The amount of acetylcholine released from the cortex and hippocampus of old rats was significantly reduced. In the presence of scopolamine and AFDX 384 but not of pirenzepine, the acetylcholine release was significantly higher in the old than the young rats, suggesting that changes in presynaptic M2/M4 muscarinic receptor function occur with ageing in the two brain regions. Cognitive capacities were evaluated using two different behavioural tasks: object recognition and passive avoidance response. Old rats were unable to discriminate between familiar and novel objects and had impaired performance in the passive avoidance test. AFDX 384 restored the performance in both tests. Furthermore, in young rats AFDX 384 reversed the impairment of both object recognition and passive avoidance response induced by scopolamine. The effect of AFDX 384 on acetylcholine release and behaviour in the old rats offers further support to a relationship between the age-related cholinergic hypofunction and cognitive impairment and indicates the blockade of presynaptic muscarinic receptors as a possible selective target for therapeutic strategies aimed at improving age-associated memory deficits.
AuthorsM G Vannucchi, C Scali, S R Kopf, G Pepeu, F Casamenti
JournalNeuroscience (Neuroscience) Vol. 79 Issue 3 Pg. 837-46 (Aug 1997) ISSN: 0306-4522 [Print] UNITED STATES
PMID9219946 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Parasympatholytics
  • AFDX 384
  • Pirenzepine
  • Scopolamine Hydrobromide
  • Acetylcholine
Topics
  • Acetylcholine (metabolism)
  • Aging (drug effects)
  • Animals
  • Cerebral Cortex (drug effects)
  • Male
  • Memory (drug effects)
  • Parasympatholytics (pharmacology)
  • Pirenzepine (analogs & derivatives, pharmacology)
  • Rats
  • Rats, Wistar
  • Scopolamine Hydrobromide (pharmacology)
  • Task Performance and Analysis

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: