AF-DX-116, A PRESYNAPTIC MUSCARINIC RECEPTOR ANTAGONIST, POTENTIATES THE EFFECTS OF GLUCOSE AND REVERSES THE EFFECTS OF INSULIN ON MEMORY

Male Swiss mice were tested 24 h after training in a one-trial step-th rough inhibitory avoidance task. Low subeffective doses of D-(+)-gluco se (10 mg/kg, ip), but not its stereoisomer L-(-)-glucose (30 mg/kg, i p), administered immediately after training, and AF-DX 116 (0.3 mg/kg, ip), a presynaptic muscarinic receptor antagonist, given 10 min after training, interact to improve retention. Insulin (8 IU/kg, ip) impair ed retention when injected immediately after training, and the effects were reversed, in a dose-related manner, by AF-DX 116 (0.3, 1.0, or 3 .0 mg/kg, ip) administered 10 min following insulin. Since AF-DX 116 p ossibly blocks autoreceptors mediating the inhibition of acetylcholine release from cholinergic nerve terminals, the present data support th e view that changes in the central nervous system glucose availability , subsequent to modification of circulating glucose levels, influence the activity of central cholinergic mechanisms involved in memory stor age of an inhibitory avoidance response in mice. (C) 1998 Academic Pre ss.