5,7-DHT-induced hippocampal 5-HT depletion attenuates behavioural deficits produced by 192 IgG-saporin lesions of septal cholinergic neurons in the rat.
Adult Long-Evans male rats sustained injections of 5,7-dihydroxytryptamine into the fimbria-fornix (2.5 microg/side) and the cingular bundle (1.5 microg/side) and/or to intraseptal injections of 192 IgG-saporin (0.4 microg/side) in order to deprive the hippocampus of its serotonergic and cholinergic innervations, respectively. Sham-operated rats were used as controls. The rats were tested for locomotor activity (postoperative days 18, 42 and 65), spontaneous T-maze alternation (days 20-29), beam-walking sensorimotor (days 34-38), water maze (days 53-64) and radial maze (days 80-133) performances. The cholinergic lesions, which decreased the hippocampal concentration of ACh by about 65%, induced nocturnal hyperlocomotion, reduced T-maze alternation, impaired reference-memory in the water maze and working-memory in the radial maze, but had no effect on beam-walking scores and working-memory in the water maze. The serotonergic lesions, which decreased the serotonergic innervation of the hippocampus by about 55%, failed to induce any behavioural deficit. In the group of rats given combined lesions, all deficits produced by the cholinergic lesions were observed, but the nocturnal hyperlocomotion and the working-memory deficits in the radial maze were attenuated significantly. These results suggest that attenuation of the serotonergic tone in the hippocampus may compensate for some dysfunctions subsequent to the loss of cholinergic hippocampal inputs. This observation is in close concordance with data showing that a reduction of the serotonergic tone, by pharmacological activation of somatodendritic 5-HT(1A) receptors on raphe neurons, attenuates the cognitive disturbances produced by the intrahippocampal infusion of the antimuscarinic drug, scopolamine. This work has been presented previously [Serotonin Club/Brain Research Bulletin conference, Serotonin: From Molecule to the Clinic (satellite to the Society for Neuroscience Meeting, New Orleans, USA, November 2-3, 2000)].
Lehmann
Olivia
O
LN2C, UMR 7521 CNRS/Université Louis Pasteur, IFR de Neurosciences 37, 12 rue Goethe, F-67000 Strasbourg, France.
Bertrand
Fabrice
F
Jeltsch
Hélène
H
Morer
Martine
M
Lazarus
Christine
C
Will
Bruno
B
Cassel
Jean-Christophe
JC
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D018678:Cholinergic Agents / Q000494:pharmacology; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D003714:Denervation; D004347:Drug Interactions; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000922:Immunotoxins / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009699:N-Glycosyl Hydrolases; D009434:Neural Pathways / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D004856:Postural Balance / Q000187:drug effects / Q000502:physiology; D011903:Raphe Nuclei / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012686:Septal Nuclei / Q000293:injuries / Q000378:metabolism / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D054789:Ribosome Inactivating Proteins, Type 1; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D000110:Acetylcholinesterase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins; D000109:Acetylcholine