Hebb-Williams performance and scopolamine challenge in rats with partial immunotoxic hippocampal cholinergic deafferentation.
Recent studies suggested that the cholinergic innervation of the hippocampus is not crucial for spatial learning, but it might be important for other forms of learning. This study assessed the effects of partial immunotoxic cholinergic lesions in the medial septum and concurrent scopolamine challenge in a complex learning task, the Hebb-Williams maze. Long-Evans rats were given intraseptal injections of 192 IgG-saporin (SAPO). Rats injected with phosphate-buffered saline (PBS) served as controls. Starting 25 days after surgery, behavioural performance was assessed in the Hebb-Williams maze test without prior or after injection of scopolamine (0.17 or 0.5 mg/kg, i.p.). In SAPO rats, histochemical analysis showed a 40-45% decrease in the density of hippocampal AChE staining. The number of ChAT-positive cell bodies in the medial septum was also significantly decreased (-56%) and there was a non-significant reduction of the number of parvalbumine-positive neurons. The behavioural results demonstrated that the lesions induced small but significant learning deficits. At 0.17 mg/kg, scopolamine produced more impairments in SAPO rats than in PBS-injected rats, suggesting an additive effect between the partial lesion and the drug. These observations indicate that the Hebb-Williams test may be more sensitive to alterations of septohippocampal cholinergic function, than radial- or water-maze tasks. They also show that subtle learning deficits can be detected after partial lesions of the cholinergic septohippocampal pathways. Finally, the data from the scopolamine challenge are in keeping with clinical results showing higher sensitivity to muscarinic blockade in aged subjects in whom weaker cholinergic functions can be presumed.
Marques Pereira
Patricia
P
Laboratoire de Neurosciences Comportementales et Cognitives, UMR 7521, CNRS-Université Louis Pasteur, IFR 37, 12, rue Goethe, F-67000 Strasbourg, France.
Cosquer
Brigitte
B
Schimchowitsch
Sarah
S
Cassel
Jean-Christophe
JC
D000109:Acetylcholine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D020667:Diagonal Band of Broca / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects* / Q000293:injuries; D007150:Immunohistochemistry / Q000379:methods; D000922:Immunotoxins / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009699:N-Glycosyl Hydrolases; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012601:Scopolamine / Q000494:pharmacology*; D012688:Septum Pellucidum / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D018727:Muscarinic Antagonists; D010320:Parvalbumins; D054789:Ribosome Inactivating Proteins, Type 1; D012601:Scopolamine; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine