Long-term effects of neonatal basal forebrain cholinergic lesions on radial maze learning and impulsivity in rats.
We examined long-term behavioural effects of neonatal lesions of the cholinergic basal forebrain obtained by intracerebroventricular injections of 192 IgG saporin (192 IgG-Sap). Five-month-old Wistar male rats (injected with 192 IgG-Sap or phosphate-buffered saline on postnatal day 7) were tested using operant chambers with two nose-poking holes, delivering one food pellet immediately or five pellets after a delay. The length of delay progressively increased over days (from 0 to 100 s). When compared with controls, 192 IgG-Sap rats showed a slight preference for smaller immediate over larger delayed rewards, thus indicating elevated intolerance to delay (i.e. more impulsivity). Sibling animals were tested in a computerized radial maze (baited vs. nonbaited arm procedure). 192 IgG-Sap rats appeared slower than controls in accomplishing the task. The neonatal 192 IgG-Sap lesion did not alter cortical levels of serotonin and/or its metabolites, but induced a marked cortical cholinergic loss. Our data suggest that a prolonged basal forebrain cholinergic hypofunction produces (i) an impairment in cognitive performances that is detectable only when highly complex tasks are used; (ii) a slight enhancement of the impulsive behavioural profile. This animal model may thus be useful to investigate some cognitive deficits and other secondary symptoms seen in Alzheimer's disease.
Scattoni
Maria L
ML
Section of Behavioural Neuroscience, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy.
Adriani
Walter
W
Calamandrei
Gemma
G
Laviola
Giovanni
G
Ricceri
Laura
L
D000544:Alzheimer Disease / Q000139:chemically induced / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018678:Cholinergic Agents; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D000922:Immunotoxins; D007175:Impulsive Behavior / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D009699:N-Glycosyl Hydrolases; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012701:Serotonin / Q000378:metabolism
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D012701:Serotonin; D002795:Choline O-Acetyltransferase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins