Neurotransmitter interactions in the control of spatial memory and exploratory activity in the rat

Abstract

The role of the central cholinergic system in learning and memory is well established, with many investigations reporting that central cholinergic hypofunction is correlated with impaired performance on various behavioural tasks, whereas improved performance is often observed with elevated cholinergic function. Attempts to enhance cholinergic activity have generally taken one of the following approaches: precursor manipulation, elevation of endogenous acetylcholine (ACh) levels via inhibition of acetylcholinesterase (AChE), and activation of postsynaptic receptors using cholinergic agonists. These strategies have met with limited clinical success. An alternate method to elevate cholinergic neurotransmission involves manipulation of the presynaptic receptor. Data from pharmachological and physiological investigations have demonstrated elevated ACh levels following administration of muscarinic ACh type-2 (M2) receptor antagonists such as AFDX 116, AFDX 384, BIBN 99, AQ-RA71, SCH 57590, SCH 7278.