Basal forebrain infusion of hemicholinium in rats : maze learning deficits and neuropathology.

Ten adult male Sprague-Dawley rats were infused with hemlcholinium (HC-3) using miniosmotic pumps over a 14 day period through bilateral, chronically implanted cannuli in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline.

HC-3 rats receiving implants demonstrated a signficant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannuli were located wtihin infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary tangles were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.