AGE-DEPENDENT EFFECT OF AF64A ON CHOLINERGIC ACTIVITY IN THE SEPTOHIPPOCAMPAL PATHWAY OF THE RAT-BRAIN - DECREASED RESPONSIVENESS IN AGED RATS

Our previous studies have demonstrated that intracerebroventricular (i cy) administration of low doses of ethylcholine mustard aziridinium (A F64A), up to 1.0 nmol/side, induces a reversible cholinergic deficit i n the hippocampus, paralleled by a compensatory transient increase in choline acetyltransferase (ChAT) activity in the septum [El Tamer, A., Corey, J., Wulfert, E. and Hanin, I., Neuropharmacology, 31 (1992) 39 7-402]. In the present study we have addressed the question as to whet her this effect might differ in old rats. AF64A (0.5 nmol/side) icy ad ministered to three groups of rats aged 4, 12 and 22 months, respectiv ely, induced a reduction of ChAT activity in the hippocampus to the sa me extent (-26%, -30.6% and -29.6%; P < 0.01) by 7 days post-icy injec tion. Acetylcholinesterase (AChE) was decreased to a similar extent in the 4 and 12 month old rats (-22% and -29%; P < 0.01), respectively, but remained unchanged in the 22 month old group. Whereas AChE activit y remained unchanged in the septum in all three groups of rats, ChAT a ctivity was increased significantly (+20% and +20.8%; P < 0.05 versus corresponding control group) in the 4 and 12 month old groups, respect ively. No change in ChAT activity was measured in the septum of the 22 months old group. By 14 days post-icy injection of AF64A, ChAT and AC hE activities were back to normal in all three groups and in both brai n regions studied. These results demonstrate that a difference in AF64 A's effect does exist between the 22 month old group and the youngest group. This might reflect a possible age-dependent change in the abili ty of the cholinergic system to respond to the cholinotoxicity of AF64 A, as well as in the potential of the cell bodies, at the septal level , to respond to such an insult by a compensatory mechanism such as inc reasing ChAT activity.