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5,7‐DHT‐induced hippocampal 5‐HT depletion attenuates behavioural deficits produced by 192 IgG‐saporin lesions of septal cholinergic neurons in the rat
Author(s) -
Lehmann Olivia,
Bertrand Fabrice,
Jeltsch Hélène,
Morer Martine,
Lazarus Christine,
Will Bruno,
Cassel JeanChristophe
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02037.x
Subject(s) - serotonergic , cholinergic , hippocampus , morris water navigation task , endocrinology , medicine , spontaneous alternation , hippocampal formation , elevated plus maze , neuroscience , radial arm maze , t maze , saporin , psychology , 5,7 dihydroxytryptamine , water maze , hypoactivity , barnes maze , working memory , serotonin , cognition , receptor , anxiety , spatial learning , immunotoxin , antibody , psychiatry , immunology , monoclonal antibody
Adult Long–Evans male rats sustained injections of 5,7‐dihydroxytryptamine into the fimbria–fornix (2.5 µg/side) and the cingular bundle (1.5 µg/side) and/or to intraseptal injections of 192 IgG‐saporin (0.4 µg/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)].