Abstract
Rationale
In rats, 5-HT1A 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-HT1A receptors on spatial working memory.
Methods
Stimulation of septal 5-HT1A receptors was carried out by infusions targetting the medial septum of the 5-HT1A/5-HT7 receptor agonist 8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT; 0.5 or 4 µg). 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 µg 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 µg 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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Acknowledgements
The authors would like to thank wholeheartedly O. Bildstein and O. Egesi for the excellent technical assistance in the animal care. They also acknowledge E. Lilly for providing a post-doctoral fellowship to F. Bertrand and research funds to the laboratory.
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H. Jeltsch and F. Bertrand contributed equally to the work.
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Jeltsch, H., Bertrand, F., Galani, R. et al. Intraseptal injection of the 5-HT1A/5-HT7 agonist 8-OH-DPAT and working memory in rats. Psychopharmacology 175, 37–46 (2004). https://doi.org/10.1007/s00213-004-1783-0
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DOI: https://doi.org/10.1007/s00213-004-1783-0