Involvement of the septohippocampal cholinergic system in representational memory.
To develop an animal model for testing muscarinic agonists, we examined the effects of cholinergic lesions with the ethylcholine aziridinium ion (AF64A) on two types of memory tasks. The tasks provided a distinction between representational and dispositional memory that could be measured in a single paradigm. Young, male Long-Evans rats were trained in a modified T-maze to learn both a discrimination task and a paired-run alternation task. Once animals learned the tasks, they were administered either saline or AF64A (5 nmol into each hippocampus) via stereotaxic technique. One week following surgery, saline-treated animals exhibited comparable performances (P greater than 0.2) on both the discrimination task (90.0 +/- 2.6% correct) and the alternation task (79.5 +/- 5.7%). In contrast, animals treated with AF64A showed a significant impairment of performance (P less than 0.005) on the alternation task (56.1 +/- 1.7%) as compared to the discrimination task (81.6 +/- 5.0%). Performance of the alternation task was significantly lower for AF64A-treated animals than for controls (P less than 0.02). AF64A-treated animals subsequently injected with pilocarpine (1.0 mg/kg, i.p.) showed moderate improvements in performance on the alternation task, while performance on the discrimination task remained unaffected. Immunocytochemical studies of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunoreactivity indicated a loss of ChAT-positive cells in the septal region in AF64A-injected animals while TH-positive cells in the ventral tegmental area were unaffected by the treatment. The data suggest that AF64A can be used to produce selective lesions of the septohippocampal cholinergic system, which plays a greater role in representational memory than in dispositional memory.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicinal and Biological Chemistry, College of Pharmacy, University of Toledo, OH 43606.
W S
WS
Messer
J R
JR
Stibbe
M
M
Bohnett
D000818:Animals; D001388:Aziridines / Q000037:antagonists & inhibitors; D001522:Behavior, Animal / Q000187:drug effects; D002794:Choline / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000033:anatomy & histology / Q000201:enzymology / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013238:Stereotaxic Techniques; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D001388:Aziridines; D009466:Neuromuscular Blocking Agents; D010277:Parasympathomimetics; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D010862:Pilocarpine; C044894:ethylcholine aziridinium; D014446:Tyrosine 3-Monooxygenase; D002795:Choline O-Acetyltransferase; D002794:Choline