Serotonin-1A receptor activation in the median raphe nucleus improves response learning-based strategy in 192IgG saporin-induced cognitive impairments

Deficits in the translation between egocentric-allocentric strategies may become another diagnostic mark for neurodegenerative disorders, especially Alzheimer's disease. Regarding the specific regional distribution of serotonin-1A receptor in brain areas mediating allocentric (externally-centered) spatial navigation to the escape location, here we studied the effects of median raphe nucleus serotonin-1A autoreceptors stimulation, [8hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT); 4 mu g/0.5 mu l saline], of a selective cholinergic denervation by intracerebroventricular administration of the 192IgG saporin (1 mu l/each ventricle), on male Wistar rats search strategies in a Morris maze during acquisition, and before probe sessions. Despite some evidence of spatial hippocampal dependent knowledge to those PBS/Saline animals, their performance dropped to chance levels on probe trial. Therefore, we considered two probabilities and first analyzed the ability of the rats to make better use of one or more strategies. We showed statistically significant increases in the distances associated with egocentric (body-centered) non-spatial strategies, random searching in particular, in 192IgG/8OH rats, which led to their improved performance. Second, considering to what extent a shift in search strategy use improves performance indicated that 8-OH-DPAT alone did not affect learning since it appeared the related performance was impaired over days. However, the strategy choices made by 192IgG/8OH rats increased performance by more than 12% compared to 192IgG/Saline rats, an effect reversed with pre-treatment by serotonin-1A receptor antagonist, N[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide (WAY 100635). The results strongly suggest the potential role of serotonergic system, via the serotonin-1A receptors, in spatial navigation. We argue that the receptors are of interest as therapeutic targets that can be used against age-related cognitive decline.

Automated summary

The study examined the distribution of serotonin-1A receptors in brain areas mediating externally-centered spatial navigation in rats, as well as the effects of median raphe nucleus serotonin-1A autoreceptors in selective cholinergic denervation. The results suggest that the serotonergic system, through the serotonin-1A receptors, plays a crucial role in spatial navigation, indicating potential therapeutic targets for age-related cognitive decline.