title: Behavioral and biochemical effects of early postnatal cholinergic lesion in the hippocampus.
abstract: The effects of early postnatal (PD 8) intracerebroventricular injection of ethylcholine mustard aziridinium ion (AF64A) on development of open-field and cognitive behaviors and cholinergic markers in several brain areas were examined in the rat. The cholinotoxin was bilaterally administered in a dose range of 0.25 to 2.0 nmol. In the open-field tests, the cholinergic lesion caused a dose-dependent increase in activity at 20 days of age, while it resulted in lengthened latency to initiate exploration and decreased rearing activity at adulthood. Hole-board spatial learning was severely inhibited in adult age. The biochemical activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the hippocampus was markedly decreased in a dose-dependent manner, but was unchanged in the neocortex and striatum. Histochemical staining of AChE-positive fibers revealed a severe cholinergic denervation of the granular and pyramidal cell layers of the hippocampus. The results showed that a selective cholinergic deafferentation of the hippocampus at a critical stage of development leads to long-lasting abnormal open-field and spatial learning behaviors.
authors.affiliation: Central Research Division, University of Postgraduate Medicine, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Gáspár
authors.forename: M
authors.initials: M
authors.lastname: Heeringa
authors.forename: E
authors.initials: E
authors.lastname: Markel
authors.forename: P G
authors.initials: PG
authors.lastname: Luiten
authors.forename: C
authors.initials: C
authors.lastname: Nyakas
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001388:Aziridines; D015415:Biomarkers / Q000737:chemistry; D002794:Choline / Q000031:analogs & derivatives; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003216:Conditioning, Operant / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology*; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology*; D006651:Histocytochemistry; D008297:Male; D009466:Neuromuscular Blocking Agents; D051381:Rats; D011919:Rats, Inbred Strains; D013037:Spatial Behavior; D013997:Time Factors
chemical_list: D001388:Aziridines; D015415:Biomarkers; D009466:Neuromuscular Blocking Agents; C044894:ethylcholine aziridinium; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D002794:Choline