Activation of septal 5-HT1A receptors alters spatial memory encoding, interferes with consolidation, but does not affect retrieval in rats subjected to a water-maze task.
Using Long-Evans rats tested in a water maze, this study assessed the role of 5-HT1A/5-HT7 receptors of the medial septum in encoding, consolidation, and retrieval of spatial information. The testing protocol (acquisition: daily four-trial sessions over three consecutive days; retention: probe trial on day 4) was first validated by showing that intraseptal infusions of lidocaine (LIDO; 40 microg/0.5 microL) disrupted acquisition and retrieval of the task. 8-OH-DPAT (4 microg/0.5 microL) infused before each acquisition session prevented learning/retention of the platform location, an effect attenuated by pretreatment with the 5-HT1A receptor antagonist WAY 100635. With the 5-HT7 antagonist SB 269970, the 8-OH-DPAT-induced acquisition deficit seemed attenuated, but there was no subsequent retention. When infused immediately, 1, 4, or 6 h after each acquisition session, 8-OH-DPAT did not hinder consolidation. When the infusions were performed 2 h postacquisition, however, consolidation was disrupted. Finally, when infused before a probe trial after drug-free acquisition, 8-OH-DPAT had no effect, suggesting no interference with retrieval processes. We also established that 8-OH-DPAT had no effects when the platform was visible, and altered neither home-cage activity nor anxiety-related behavior (elevated plus-maze). Altogether, these results show that 5-HT1A receptors in the septal region contribute both to declarative-like information encoding and subsequently, within a given postacquisition time window, to its consolidation. They do not participate in the retrieval of recently learned declarative-like information. These observations suggest that 5-HT1A receptors of the medial septum contribute to a serotonin-mediated mechanism involved in the encoding and consolidation, not the retrieval of spatial hippocampal-dependent knowledge. These results might have some relevance to approaches aimed at modifying serotonergic functions in the brain for the treatment of disorders such as depression, anxiety, post-traumatic stress, and amnesia.
Koenig
Julie
J
LINC UMR 7191, CNRS-Université Louis Pasteur, Institut Fédérératif de Recherche 37-GDR CNRS 2905, 12 rue Goethe, Strasbourg, France.
Cosquer
Brigitte
B
Cassel
Jean-Christophe
JC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001522:Behavior, Animal; D003463:Cues; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D020665:Septum of Brain / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*
D000779:Anesthetics, Local; D010879:Piperazines; D011725:Pyridines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008012:Lidocaine