AF64A (ETHYLCHOLINE MUSTARD AZIRIDINIUM) IMPAIRS ACQUISITION AND PERFORMANCE OF A SPATIAL, BUT NOT A CUED WATER MAZE TASK - RELATION TO CHOLINERGIC HYPOFUNCTION
Kd. Opello et al., AF64A (ETHYLCHOLINE MUSTARD AZIRIDINIUM) IMPAIRS ACQUISITION AND PERFORMANCE OF A SPATIAL, BUT NOT A CUED WATER MAZE TASK - RELATION TO CHOLINERGIC HYPOFUNCTION, Physiology & behavior, 54(6), 1993, pp. 1227-1233
The cholinergic neurotoxin AF64A (ethylcholine mustard aziridinium) pr
oduced alterations in a spatial but not a nonspatial cognitive task fo
llowing ICV injection. AF64A impaired acquisition and performance in t
he standard Morris water maze task, evidenced by significantly longer
latencies to find the submerged platform. However, the AF64A group exh
ibited shorter latencies and more direct paths to the target at the en
d of training, which suggests acquisition of efficient search strategi
es and a sparing of procedural memory. However, the AF64A group spent
significantly less time in the target quadrant during the probe trial
than the CSF group. This suggests a failure to learn the specific loca
tion of the target and impaired declarative memory processes. In contr
ast, AF64A did not affect performance of a cued MWM task that did not
involve spatial memory processing, demonstrating the absence of motori
c, sensory, or motivational impairments. The AF64A-induced behavioral
deficits were associated with a) a significant decrease in high affini
ty choline transport (HAChT), b) reduced concentrations of 5-HT and 5-
HIAA, and c) an increased ratio of 5-HIAA/5HT in the HPC. There were n
o changes in choline uptake in the gustatory cortex, the amygdala, or
the striatum. Percent time in the target quadrant during the probe tri
al was significantly correlated with HAChT in the HPC. There were no c
orrelations between any of the behavioral measures and HAChT in the st
riatum, gustatory cortex, or the amygdala, or between serotonergic or
noradrenergic parameters in the HPC. These data suggest that AF64A pro
duces cognitive deficits in spatial tasks that are correlated with the
cholinergic hypofunction induced by the compound.