Spatial memory alterations by activation of septal 5HT 1A receptors: no implication of cholinergic septohippocampal neurons.
BACKGROUND
In rats, activation of medial septum (MS) 5-HT(1A) receptors with the 5-HT(1A)/5-HT(7) receptor agonist 8-OH-DPAT disrupts encoding and consolidation, but not retrieval of a spatial memory in the water maze task. These findings might be explained by an action of 8-OH-DPAT on 5-HT(1A) receptors located on cholinergic neurons which the drug could transiently hyperpolarise. If so, selective damage of these neurons should mimic the effects of 8-OH-DPAT, or, at least, synergistically interfere with them.


METHODS
To test this hypothesis, rats were subjected to intraseptal infusions of 8-OH-DPAT (or phosphate-buffered saline) during acquisition of a water maze task before and/or after 192 IgG-saporin-induced MS cholinergic lesion (vs. sham-operated).


RESULTS
We confirmed that only pre-acquisition intraseptal 8-OH-DPAT infusions prevented learning and subsequent drug-free retrieval of the platform location in intact rats and found that (1) the cholinergic lesion did not prevent recall of the platform location, and (2) the impairing effects of 8-OH-DPAT were similar in sham-operated and lesioned rats, whether naïve or not, to the task before lesion surgery.


CONCLUSIONS
An action of 8-OH-DPAT on only MS cholinergic neurons is not sufficient to account for the drug-induced memory impairments. A concomitant 8-OH-DPAT-induced hyperpolarisation of cholinergic and/or GABAergic and/or glutamatergic neurons (intact rats), or of only GABAergic and/or glutamatergic ones after cholinergic lesion, might be necessary to obliterate task acquisition, confirming that, in the MS, (1) the three neuronal populations could cooperate to process hippocampal-dependent information, and (2) non-cholinergic septohippocampal neurons might be more important than cholinergic ones in serotonin-induced modulation of hippocampus-dependent memory processing.
Laboratoire d'Imagerie et de Neurosciences Cognitives, FRE 3289, Université de Strasbourg-CNRS, Institut Fédérératif de Recherche 37-GDR CNRS 2905, 12 rue Goethe, 67000, Strasbourg, France. jcassel@unistra.fr
Julie
J
Koenig
Lucas
L
Lecourtier
Brigitte
B
Cosquer
Patricia Marques
PM
Pereira
Jean-Christophe
JC
Cassel
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism; D003463:Cues; D003714:Denervation / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007263:Infusions, Parenteral; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D009043:Motor Activity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage; D000076985:Saporins; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D054789:Ribosome Inactivating Proteins, Type 1; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000076985:Saporins; D000109:Acetylcholine