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  • Title: Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats.
    Author: Jeltsch H, Bertrand F, Galani R, Lazarus C, Schimchowitsch S, Cassel JC.
    Journal: Psychopharmacology (Berl); 2004 Aug; 175(1):37-46. PubMed ID: 15014926.
    Abstract:
    RATIONALE: In rats, 5-HT(1A) receptors are present in the septal region, e.g. on cholinergic neurons of the medial septum, where they might be a substrate for cognitively relevant interactions between cholinergic and serotonergic systems. OBJECTIVE: The present experiment assessed the effects of the stimulation of septal 5-HT(1A) receptors on spatial working memory. METHODS: Stimulation of septal 5-HT(1A) receptors was carried out by infusions targetting the medial septum of the 5-HT(1A)/5-HT(7) receptor agonist 8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT; 0.5 or 4 microg). Spatial memory was assessed in a water maze using a protocol placing emphasis on spatial working memory. The location of the hidden platform was changed every day and performance was assessed on two consecutive trials each day. RESULTS: In comparison to vehicle injections, the intraseptal infusion of 4 microg 8-OH-DPAT impaired performance significantly: rats treated with 8-OH-DPAT exhibited increased distances to reach the hidden platform on both trials 1 and 2. Rats infused with 0.5 microg showed similar changes that failed to be significant. Such effects were not observed when the platform was visible. CONCLUSIONS: These results extend those of a previous experiment which showed that intraseptal injections of 8-OH-DPAT impaired spatial reference memory. Based on the characteristics of the observed deficits, it is suggested that the 8-OH-DPAT-induced impairment, rather than being only the result of a true alteration of working memory, might reflect a more global cognitive deficiency in which alteration of general memory capacities may be biased by disrupted search strategies/exploration and/or dysfunctions of attention.
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