AF64A (ethylcholine mustard aziridinium) impairs acquisition and performance of a spatial, but not a cued water maze task: relation to cholinergic hypofunction.
The cholinergic neurotoxin AF64A (ethylcholine mustard aziridinium) produced alterations in a spatial but not a nonspatial cognitive task following ICV injection. AF64A impaired acquisition and performance in the standard Morris water maze task, evidenced by significantly longer latencies to find the submerged platform. However, the AF64A group exhibited shorter latencies and more direct paths to the target at the end of training, which suggests acquisition of efficient search strategies 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 location of the target and impaired declarative memory processes. In contrast, AF64A did not affect performance of a cued MWM task that did not involve spatial memory processing, demonstrating the absence of motoric, sensory, or motivational impairments. The AF64A-induced behavioral deficits were associated with a) a significant decrease in high affinity 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 no changes in choline uptake in the gustatory cortex, the amygdala, or the striatum. Percent time in the target quadrant during the probe trial was significantly correlated with HAChT in the HPC. There were no correlations between any of the behavioral measures and HAChT in the striatum, gustatory cortex, or the amygdala, or between serotonergic or noradrenergic parameters in the HPC. These data suggest that AF64A produces cognitive deficits in spatial tasks that are correlated with the cholinergic hypofunction induced by the compound.
Opello
K D
KD
Department of Psychology, Rutgers University, New Brunswick, NJ 08903.
Stackman
R W
RW
Ackerman
S
S
Walsh
T J
TJ
D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001388:Aziridines / Q000494:pharmacology*; D002794:Choline / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D011939:Mental Recall / Q000187:drug effects* / Q000502:physiology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism; D009949:Orientation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012688:Septum Pellucidum / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013550:Swimming; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C044894:ethylcholine aziridinium; D002794:Choline; D000109:Acetylcholine; D009638:Norepinephrine